bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of chronic hypoxia on capillary flow and hematocrit in rat skeletal muscle
Authors: Fisher A. J. , Schrader N. W. , Klitzman B.
Published: December 2017

The cremasteric microcirculation was studied in rats exposed to chronic hypoxia. Control male weanling Sprague-Dawley rats (n = 8) were raised for 42-49 days at 752 mmHg. Hypoxic rats (n = 9) were reared for 3 days at 551 mmHg, 4 days at 461 mmHg, 3 days at 371 mmHg, and 31-38 days at 311 mmHg (6,000 m). Red blood cells labeled with fluorescein isothiocyanate were injected. The exposed cremaster was observed using fluorescence microscopy. Rats acutely breathed 10, 21, and 30% O2 spontaneously in random order. Hypoxia-adapted animals had greater (P less than 0.01) red cell flux (10.6 +/- 1.0 vs. 5.7 +/- 0.4/s), capillary hematocrits, capillary-to-systemic hematocrit ratios (0.42 +/- 0.02 vs. 0.33 +/- 0.02), and reduced red cell spacing (11.4 +/- 1.3 vs. 22.3 +/- 2.0 microns) than controls under 21% O2. Chronically hypoxic rats also demonstrated significantly (P less than 0.05) larger capillary diameters (6.52 +/- 0.04 vs. 6.15 +/- 0.06 microns) and greater perfused (135 +/- 5 vs. 94 +/- 3 mm/mm3) and anatomic (182 +/- 5 vs. 151 +/- 8 mm/mm3) microvessel length-densities at 21% O2. Results were generally similar for 10 and 30% O2. Bulk capillary blood flow was significantly (P less than 0.01) greater in controls (2.75 +/- 0.32 vs. 1.87 +/- 0.12 pl/s) only under 30% O2. Our experiments demonstrate that numerous physiological, in addition to anatomic, alterations can occur in the cremasteric microcirculation in response to chronic hypoxia.
Role of superoxide anion and endothelium in vasoconstrictor action of prostaglandin endoperoxide
Authors: Tesfamariam B. , Cohen R. A.
Published: December 2017

The vasoconstrictor actions of prostaglandin (PG) endoperoxide, PGH2, were examined in isolated rabbit aortic rings suspended for measurement of isometric tension. In aortic rings with an intact endothelium, PGH2 caused concentration-dependent contractions which were blocked by SQ 29548 (a PGH2-thromboxane A2 receptor blocker) or superoxide dismutase (a superoxide anion scavenger) but not by carbethoxyhexyl imidazole (a thromboxane A2 synthase inhibitor) or catalase (a hydrogen peroxide scavenger). In contrast U 46619, a thromboxane A2 mimic, caused contractions, which were blocked by SQ 29548 but not by superoxide dismutase. PGH2 caused significantly greater contractions in aortic rings without endothelium or in those with intact endothelium treated with NG-nitro-L-arginine, a nitric oxide inhibitor; these contractions were inhibited by SQ 29548 but not by superoxide dismutase. In aortic rings with endothelium contracted with phenylephrine, a subthreshold concentration of PGH2, but not U 46619, impaired relaxations to acetylcholine; the inhibition was prevented by treatment with SQ 29548 or superoxide dismutase, indicating that the abnormality of endothelial cell function was specific for PGH2. These observations indicate that PGH2 causes contractions and inhibits endothelium-dependent relaxation by a mechanism involving formation of superoxide anion, which interacts with endothelium-derived nitric oxide.
Novel technique to load indo-1 free acid into single adult cardiac myocytes to assess cytosolic Ca2+
Authors: Sollott S. J. , Ziman B. D. , Lakatta E. G.
Published: December 2017

This report introduces a novel method to load indo-1 “free acid” selectively into the cytosol of cardiac myocytes, presumably by diffusion through momentarily permeable gap junction sites during mechanical dissociation after low-Ca2+ collagenase treatment. Calibration of indo-1 fluorescence in these cells has been accomplished after subtracting average autofluorescence (AF) from time-matched non-indo-loaded cells, taking into account apparent changes in cell AF due to indo-1. There is wide variation in the degree of uncertainty of individual intracellular Ca2+ concentration ([Ca2+]i) determinations among cells, related principally to differences in cellular indo-1 content, to nonlinear aspects of the [Ca2+]-to-fluorescence ratio relationship, and to the uncertainty in the AF subtraction. Consequently, a quantitative estimate of uncertainty also may be employed in formulating weighted estimates of cytosolic [Ca2+]i. The following [Ca2+]i values in rat ventricular cells (nM; in 1 mM bathing extracellular Ca2+ concentration, 25 degrees C) are given as weighted means +/- 95% confidence intervals (unweighted values in parentheses): 138 +/- 5 (136 +/- 6, n = 44) in quiescent cells, 435 +/- 74 (482 +/- 76, n = 43) at the [Ca2+]i-transient peak during 0.5 Hz steady-state stimulation, and 760 +/- 124 (1,027 +/- 250, n = 42) at the [Ca2+]i-transient peak, postrest. Moreover, these peak [Ca2+]i values fall near the steepest portion of the force-Ca2+ curve (from intact cardiac muscle), consistent with sensitive inotropic regulation and maximal contractile reserve.
Kinetic characteristics of alpha 1-adrenergic contractions in human corpus cavernosum smooth muscle
Authors: Christ G. J. , Schwartz C. B. , Stone B. A. , Parker M. , Janis M. , Gondre M. , Valcic M. , Melman A.
Published: December 2017

Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) activation of the alpha 1-adrenergic receptor subtype in vascular smooth muscle isolated from the corpus cavernosum of impotent men. PE-induced contractions were separated into distinct phasic and tonic components, and the tonic portion was analyzed using a first-order rate equation to determine the maximal rate constant for onset of contraction (kobs max) and the maximum amplitude of the steady-state contractile response (Req max). The kobs max value in tissues from insulin-dependent diabetic patients was significantly greater than that in tissues from either noninsulin-dependent diabetics or nondiabetics. Additionally, the mean kobs max value in older patients (60-70 yr) was significantly greater than the mean kobs max value in younger patients (32-59 yr). Significant diabetes-related, but not age-related, alterations were also found in Req max. The observed changes in contractility resulted in dramatic age- and pathology-dependent alterations in the initial rate and/or magnitude of PE-induced response generation. These kinetic studies extend our previous observations at steady state and provide further evidence for heightened corporal tissue tone in the etiology of erectile dysfunction.
Lower brain stem controls cardiac ANF secretion
Authors: Jiao J. H. , Guyenet P. G. , Baertschi A. J.
Published: December 2017

The purpose of these studies was to investigate whether the central nervous system (CNS) can modulate the plasma level of atrial natriuretic factor (ANF). In anesthetized, spontaneously breathing rats, electrical stimulation was stereotaxically applied bilaterally to four medullary nuclei: 1) the rostral nucleus of the solitary tract (rNTS), 2) the intermediate portion of the NTS (iNTS), 3) the ventrolateral nucleus ambiguus (NA) 0.3 mm rostral to obex, and 4) the rostral ventrolateral medulla (RVL). Electrical stimulation of the rNTS and RVL caused a 55 +/- 18% (P less than 0.025, n = 6) and 187 +/- 80% (P less than 0.001, n = 5) increase in plasma ANF, respectively, compared with baseline (56-88 pg/ml), whereas sham stimulations had no effect on plasma ANF release. In contrast, electrical stimulation of the iNTS and the NA elicited a 35 +/- 6 (P less than 0.01, n = 7) and 31 +/- 6% (P less than 0.05, n = 5) decrease in plasma ANF, respectively. In artificially ventilated rats, unilateral electrical stimulation of the RVL induced a 94 +/- 39 (left RVL, n = 6, P less than 0.01) and 186 +/- 68% (right RVL, P less than 0.01, n = 5) increase in plasma ANF over baseline. Unilateral microinjection of L-glutamate into RVL also resulted in a 81 +/- 23% (n = 9, P less than 0.01) increase in plasma ANF compared with baseline and vehicle control injections. These results suggest that activation of the central sympathetic system potently stimulates the secretion of cardiac ANF.
Contribution of adenosine to isoproterenol-stimulated prostacyclin production in rabbit heart
Authors: Cano C. , Qureshi Z. , Carter S. , Malik K. U.
Published: December 2017

This study investigated adenosine's contribution to isoproterenol-stimulated prostacyclin production, measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output, and mechanical function in the isolated rabbit heart perfused with Krebs-Henseleit buffer. The isoproterenol-induced increase in 6-keto-PGF1 alpha was diminished by adenosine (10 microM), the A1 receptor antagonist 1,3-dipropyl, 8-cyclopentylxanthine (DPCPX 0.06 microM), and the A2 receptor agonist CGS-21680 (0.6 microM); CGS-21680 did not decrease heart rate (HR) or myocardial contractility (dP/dt(max)). The isoproterenol-induced increase in 6-keto-PGF1 alpha was potentiated by the A1 receptor agonist 1-deaza,2-chloro,N6-cyclopentyladenosine (DCCA, 0.6 microM) and the A2 receptor antagonist 3,7-dimethyl,1-propargylxanthine (DMPX, 6 microM). The isoproterenol-induced increase in dP/dt(max) and HR was diminished by adenosine, DCCA, and DMPX. DPCPX enhanced dP/dt(max) and HR and prevented the decrease by adenosine and DCCA of the isoproterenol-induced increase in HR and dP/dt(max); the increase by DCCA but not the decrease by adenosine in 6-keto-PGF1 alpha output was abolished. DMPX abolished the effect of adenosine and CGS-21680 to reduce isoproterenol-stimulated 6-keto-PGF1 alpha. These data suggest that adenosine generated in response to isoproterenol attenuates its effect on HR and dP/dt(max) through A1 receptors and on prostacyclin synthesis via A2 receptors.
Left ventricular diastolic and systolic performance during chronic experimental aortic regurgitation
Authors: Magid N. M. , Wallerson D. C. , Borer J. S. , Mukherjee A. , Young M. S. , Devereux R. B. , Carter J. N.
Published: December 2017

To study the time course of left ventricular structural and functional responses to chronic aortic regurgitation, aortic regurgitation was surgically induced in rabbits, and Doppler echocardiography was performed preoperatively and serially postoperatively for up to 2.5 yr. Twenty-five New Zealand White rabbits underwent surgical induction of aortic regurgitation and 13 control animals underwent sham operation. Left ventricular endocardial and epicardial surfaces were digitized from M-mode echocardiograms to measure the rates of change of cavity dimensions and wall thicknesses during diastolic relaxation and systolic contraction. Aortic regurgitant animals developed left ventricular dilatation and eccentric hypertrophy that remained relatively stable throughout the follow-up period. Compared with baseline values, left ventricular mass increased 120% and left ventricular internal dimension at end diastole increased 40%, whereas posterior wall thickness at end diastole and fractional shortening remained relatively stable. Left ventricular diastolic performance was enhanced at 6 mo after operation, a finding associated with increased volume load and heart rate following induction of aortic regurgitation. Diastolic performance was then reduced at 12 mo after operation and demonstrated no further decline throughout the remainder of the follow-up period. In contrast, left ventricular systolic performance was not altered following operation and remained preserved until the final assessment at up to 2.5 yr. Thus alterations in diastolic performance occurred without impairment of systolic performance during long-term follow-up of chronic experimental aortic regurgitation.
Left ventricular shape changes during the course of evolving heart failure
Authors: Sabbah H. N. , Kono T. , Stein P. D. , Mancini G. B. , Goldstein S.
Published: December 2017

The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.
Oxygen diffusion in hamster striated muscle: comparison of in vitro and near in vivo conditions
Authors: Meng H. , Bentley T. B. , Pittman R. N.
Published: December 2017

To investigate the suggestion of A. S. Popel, R. N. Pittman, and M. L. Ellsworth [Am. J. Physiol. 256 (Heart Circ. Physiol. 25): H921-H924, 1989] that Krogh's diffusion coefficient for O2 in vivo might be an order of magnitude higher than in vitro, O2 diffusion coefficient (DO2) and resting O2 consumption were measured on hamster retractor muscle in vitro and under near in vivo conditions where the muscle remained attached to the animal but the arterial inflow was occluded just before measurement. Experiments were performed on two groups of animals, differing in weight and age. We found that DO2 determined in vitro (extrapolated to 37 degrees C) was 1.81 +/- 0.12 x 10(-5) cm2/s for group I (smaller and younger), which was not significantly different from the value (2.00 +/- 0.08 x 10(-5) cm2/s) determined in group II. In both groups, DO2 under near in vivo conditions tended to be 10-15% larger than the value in vitro, although this trend did not reach statistical significance. It is unlikely that this trend is large enough to reconcile the inconsistency between theoretical and experimental determinations of O2 diffusion from the arteriolar network of this tissue.
cGMP pathway and mechanical properties of carotid artery wall in WKY rats and SHR: role of endothelium
Authors: Mourlon-Le Grand M. C. , Benessiano J. , Levy B. I.
Published: December 2017

We measured the static mechanical properties and tissue guanosine 3',5'-cyclic monophosphate (cGMP) content in the carotid artery of 16- to 18-wk-old Wistar-Kyoto (WKY) rats and age-matched spontaneously hypertensive rats (SHR). Carotid compliance (CC) and tissue cGMP measurements were performed under control conditions with intact endothelium (E+), after local incubation with methylene blue (10(-5) M, 20 min), and after mechanical removal of the endothelium (E-). Under control conditions, CC was lower in SHR than in WKY rats (P less than 0.01) and carotid cGMP level was higher in SHR than in WKY rats (30.34 +/- 3.69 vs. 19.72 +/- 2.28 fmol/mg tissue; P less than 0.02). Methylene blue induced no significant change in CC in both strains and produced a similar decrease in carotid cGMP in WKY rats by 88% (P less than 0.001) and in SHR by 94% (P less than 0.001). Endothelium removal induced a similar increase in CC relative to control conditions (P less than 0.01, in both strains) but reduced cGMP content by 28% in WKY rats (P less than 0.02) and by 90% in SHR (P less than 0.001), i.e., a significantly higher reduction in SHR than in WKY rats (P less than 0.001). Despite a higher vasomotor tone, the "cGMP pathway" seems to be more activated in the SHR than in the WKY rat. Our results suggest that the mechanism involved in cGMP synthesis regulation in the SHR is endothelium dependent. This may be interpreted as an insufficient endothelium-dependent compensatory phenomenon of local regulation against genetic abnormalities.
Oxidant stress alters Na+ pump and Na(+)-K(+)-Cl- cotransporter activities in vascular endothelial cells
Authors: Elliott S. J. , Schilling W. P.
Published: December 2017

We have previously shown that oxidant stress activates Ca(2+)-dependent K+ efflux in pulmonary vascular endothelial cells. The present study was performed to determine the effect of oxidant stress on Na+ and K+ homeostasis using the radiotracers, 22Na+ and 86Rb+. Cellular ion contents at equilibrium were determined after incubation of cells with tert-butyl hydroperoxide (t-BOOH; 0.4 mM) for various durations. Cell content of 86Rb+ was unchanged through incubation periods of 2 h but was significantly decreased at 3 h, whereas cell content of 22Na+ progressively increased with increasing incubation duration. The effect of t-BOOH on Na+ pump and Na(+)-K(+)-Cl- cotransporter activities was examined via measurement of 86Rb+ influx in the absence or presence of ouabain and bumetanide, respectively. Oxidant stress time dependently increased ouabain-sensitive 86Rb+ influx, with little alteration in specific ouabain binding. In contrast, bumetanide-sensitive 86Rb+ influx was decreased by incubation with the oxidant. These findings suggest that the oxidant-induced increase in cellular Na+ content is associated with increased plasmalemmal Na(+)-K(+)-adenosinetriphosphatase activity. Furthermore, inward ion movement via the bumetanide-sensitive pathway is decreased, suggesting that oxidant stress inhibits the Na(+)-K(+)-Cl- cotransporter.
Metabolism of angiotensin I by different tissues in the intact animal
Authors: Danser A. H. , Koning M. M. , Admiraal P. J. , Derkx F. H. , Verdouw P. D. , Schalekamp M. A.
Published: December 2017

To quantify regional conversion of angiotensin (ANG) I to ANG II and its degradation to peptides other than ANG II, monoiodinated 125I-labeled ANG I was given to anesthetized pigs by constant infusion into the left cardiac ventricle. At steady state, blood samples were taken from the aorta and various regional veins. Distribution volume of ANG I appeared to be 24% of body weight. After angiotensin-converting enzyme (ACE) inhibitor treatment, fractional ANG I metabolism (fraction of arterially delivered ANG I that was metabolized during a single passage of blood) was 10% in the lungs (conversion 4%), compared with 56% in the combined systemic vascular beds (conversion 1%). Fractional ANG I metabolism during ACE inhibition was 93% in the kidney; 50-70% in myocardium, skeletal muscle, head, and skin; 21% in the left cardiac cavity; and 14% in the right cardiac cavity. Without ACE inhibition, fractional ANG I metabolism was 29% in the lungs (conversion 25%); 49% in the combined systemic vascular beds (conversion 10%); 38% in the left cardiac cavity (conversion 11%); and 14% in the right cardiac cavity (conversion 0%). It may thus be concluded that 1) extrapulmonary vascular beds make an important contribution to the conversion of circulating ANG I and 2) there is rapid extrapulmonary ANG I degradation that does not depend on ANG I-II conversion.
Acute hypertension and sympathetic stimulation: local heterogeneous changes in cerebral blood flow
Authors: Tuor U. I.
Published: December 2017

The local influence of sympathetic stimulation on the cerebral circulation during acute hypertension was investigated in anesthetized rats. From initial studies, intravenously administered angiotensin II was selected as the pressor agent. Local cerebral blood flow was measured with [14C]iodoantipyrine autoradiography during 1) unilateral electrical stimulation of the superior cervical ganglion plus moderate hypertension [mean arterial blood pressure (MABP) 162 +/- 2 mmHg], 2) unilateral stimulation plus severe hypertension (MABP 177 +/- 4 mmHg), and 3) unilateral preganglionic sympathetic nerve section (denervated) plus severe hypertension (MABP 186 +/- 4 mmHg). During moderate hypertension, blood flow was rather homogeneous and sympathetic stimulation produced modest (7-15%) regionally specific reductions in flow ipsilateral to the stimulation (P less than 0.05). During severe hypertension: 1) focal areas of marked hyperemia occurred throughout the brain, 2) local blood flow was similar within innervated and denervated hemispheres, and 3) with sympathetic stimulation the volume of hyperemic tissue was reduced ipsilaterally and blood flow was decreased by 7-25% in areas of basal ganglia, cerebral cortex, limbic system and thalamus. To conclude, 1) the local cerebral autoregulatory response is highly dependent on whether the area becomes hyperperfused and 2) sympathetic stimulation decreases brain blood flow by modestly reducing local tissue perfusion and by lessening the volume of extreme hyperemia.
Effects of arterial hypertension on myocardial recovery after ischemic injury
Authors: Elbeery J. R. , Williams R. F. , Rankin J. S. , Glower D. D. , Sabiston D. C. , Van Trigt P.
Published: December 2017

Although improved surgery, angioplasty, and thrombolysis have made early revascularization of ischemic myocardium commonplace, the effects of arterial hypertension on myocardial recovery remain unclear. Therefore eight conscious dogs were instrumented to measure left ventricular transmural pressure and myocardial segment length in the left anterior descending (LAD) coronary distribution. Reversible ischemic injury was produced by two 15-min LAD occlusions separated by 4 days of reperfusion, with each dog randomly receiving either phenylephrine or placebo infusion for 30 min beginning 1 h after reperfusion. With ischemia, systolic myocardial performance fell to 14.3 +/- 3.7% of control and required greater than 48 h to recover. Compared with placebo, phenylephrine significantly depressed recovery of systolic function assessed by systolic shortening (57 +/- 12 vs. 85 +/- 13% control) or the area under the stroke work vs. end-diastolic length relationship (62 +/- 14 vs. 93 +/- 7% control) (both P less than 0.05). These data imply that ischemically injured myocardium is highly sensitive to arterial hypertension and that ventricular loading is a major determinant of the rate of myocardial recovery.
Effect of methylene blue on vasoreactivity in dog lung
Authors: Hofman W. F. , el-Kashef H. A. , Endredi J. , Ehrhart I. C.
Published: December 2017

We examined the effect of methylene blue (MB), a putative inhibitor of guanylate cyclase (GC) activation by endothelium-derived relaxing factor (EDRF) and nitrovasodilator compounds, on vascular tone and reactivity to vasoactive substances in the isolated, blood-perfused canine lower left lung lobe. Lobar vascular resistance was partitioned into arterial and venous segments by venous outflow occlusion. Because MB did not alter vasoconstriction to either serotonin or acetylcholine (P greater than 0.05) except after cyclooxygenase inhibition (COI), we determined the effectiveness of MB as an inhibitor of GC activation by nitrovasodilators. Lobes were given graded bolus doses of nitroglycerin (GTN), sodium nitroprusside (SNP), and bradykinin (BK) at baseline vascular tone, after COI, and after vascular tone was raised by either U-46619, a thromboxane analogue, or MB infusion. GTN and BK but not SNP induced dose-dependent vasodilation when vascular tone was raised by U-46619. However, when vascular tone was increased to a similar level by 30 mg MB and 0.5 mg/min infusion, vasodilation to GTN, SNP, and BK was enhanced from U-46619 infusion. In contrast to MB, NG-nitro-L-arginine, a putative inhibitor of EDRF synthesis, diminished vasodilation to BK in cyclooxygenase-inhibited lobes with elevated vascular tone. Because MB potentiated vasodilation to GTN, SNP, and BK, it is questionable whether MB is an effective inhibitor of vasodilation to nitrovasodilators or BK in the isolated, blood-perfused canine lung.
EDTA influences reactivity of isolated aorta from hypercholesterolemic rabbits
Authors: Simon B. C. , Cohen R. A.
Published: December 2017

Pages H1606–H1610: B. C. Simon and R. A. Cohen. “EDTA influences reactivity of isolated aorta from hypercholesterolemic rabbits.” Page H1608: Figures 1 and 2 should read as the following.

(See PDF)
Coronary microvascular response to endothelin is dependent on vessel diameter and route of administration
Authors: Lamping K. G. , Clothier J. L. , Eastham C. L. , Marcus M. L.
Published: December 2017

Endothelin is a 21-amino acid peptide originally isolated from vascular endothelial cells. In the present study, we examined the effect of topical and intracoronary administration of endothelin-1 on the coronary microcirculation and the effect of inhibition of cyclooxygenase on the microvascular response to intracoronary endothelin. In anesthetized dogs (n = 39), the coronary microcirculation was visualized using stroboscopic epi-illumination synchronized to the cardiac cycle. Topical application of endothelin [(5 x 10(-9) to 10(-8) M] constricted all arteries and arterioles with the degree of constriction inversely related to vessel size. Coronary veins and venules did not constrict to endothelin. Topical application of EDTA (10 mg/ml) reversed the constriction to endothelin in arterioles of all sizes. In contrast, intracoronary administration of endothelin (10(-8) to 10(-7) M) produced dilation of small arterioles (less than 130 microns) and no response of large arterioles (greater than 130 microns). The response of small arterioles to intracoronary endothelin was not altered by inhibition of cyclooxygenase with indomethacin (5 mg/kg); however, large arterioles constricted. Thus the coronary microvascular response to endothelin is dependent on the route of administration. Constriction of arteries and arterioles of all sizes to endothelin is dependent on extracellular calcium. Vasodilator prostaglandins may be released in response to intracoronary administration of endothelin predominantly in larger vessels. Thus the differential response to endothelin with topical and intracoronary administration may reflect a diffusional barrier of the endothelium or release of endothelium-derived relaxing factor and prostaglandins in response to endothelin.
Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs
Authors: Lefer D. J. , Nakanishi K. , Vinten-Johansen J. , Ma X. L. , Lefer A. M.
Published: December 2017

Endothelial dysfunction is a prominent occurrence in coronary arteries after myocardial ischemia and reperfusion. However, this has not been studied in coronary veins. Endothelium-dependent vasorelaxation was studied in cardiac venous rings obtained from dogs subjected to 60 min of coronary artery occlusion followed by 270 min of reperfusion, as well as from dogs subjected to sham ischemia-reperfusion. Myocardial ischemia resulted in a 96 +/- 2% decrease in coronary flow to the ischemic area 60 min after occlusion of the left anterior descending (LAD) coronary artery, which led to a significant degree of cardiac necrosis (i.e., 32.9 +/- 3.9% of area at risk). Cardiac venous rings isolated from sham ischemia-reperfusion dogs relaxed 68 +/- 3% to 200 microM ADP, 65 +/- 3% to 2 microM A23187, and 76 +/- 4% to 200 microM sodium nitrite (NaNO2). Corresponding values for cardiac venous rings isolated from ischemic-reperfused dogs were 32 +/- 3% for 200 microM ADP (P less than 0.01 vs. sham), 31 +/- 3% for 2 microM A23187 (P less than 0.01 vs. sham), and 74 +/- 3% for 200 microM NaNO2 (NS from sham). In rings from control dogs, vasorelaxation to ADP and A23187 was markedly inhibited by 4 mM NG-methyl-L-arginine (L-NMMA) and 10 methylene blue and restored after NG-nitro-L-arginine by 3 mM L-arginine. These results demonstrate that a significant degree of endothelial dysfunction occurred in cardiac venous rings after ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelin in thoracic inferior vena caval constriction model of heart failure
Authors: Underwood R. D. , Aarhus L. L. , Heublein D. M. , Burnett J. C.
Published: December 2017

Recent studies have found endothelin-1 (ET), a potent vasoconstrictor of endothelial cell origin, is increased in congestive heart failure (CHF) in plasma and correlates with increased atrial pressures. Additionally, it has been shown that, despite increased circulating ET concentrations in CHF, a decreased responsiveness to exogenous ET infusion exists in an experimental model of CHF induced by rapid pacing. The present study was designed to determine whether plasma ET would be increased in a model of low cardiac output congestive failure without elevated atrial pressures produced by thoracic inferior vena caval constriction (TIVCC). In addition, we sought to determine whether this model of low cardiac output would show a full vasoconstrictive response to exogenous ET infusion and whether atrial natriuretic factor (ANF) infused acutely to achieve pathophysiological concentrations would modulate the systemic and renal hemodynamic responses to exogenous ET. Dogs were studied in the anesthetized state at 8-9 days after the TIVCC or sham operation. Baseline ET levels were significantly increased in the TIVCC dogs (n = 14) compared with sham operated dogs (n = 6; 41.4 +/- 7.1 vs. 17.9 +/- 1.5 pg/ml, respectively; P less than 0.05). With exogenous ET infusion (5 ng.kg-1.min-1), an intact systemic and renal vasoconstrictor response in the TIVCC dogs was observed. ANF prevented the systemic vascular and arterial pressure responses to ET. However, the potent renal vasoconstricting action of ET was not prevented by ANF. These studies suggest that ET may play an important role in maintaining blood pressure in the setting of low cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypoxia induces endothelial cells to increase their adherence for neutrophils: role of PAF
Authors: Milhoan K. A. , Lane T. A. , Bloor C. M.
Published: December 2017

We investigated the interactions of polymorphonuclear neutrophils (PMN) and endothelial cells in myocardial ischemia using a hypoxia model. We exposed porcine aortic (PAEC) and porcine coronary microvessel (PCMEC) endothelial cells to 2% O2 for 2 h (PO2 = 53 mmHg) and measured the adherence of unstimulated neutrophils (PMN) to both control and hypoxia-conditioned endothelial cell monolayers. Hypoxia conditioning increased PMN adherence to PAEC and PCMEC by 51 and 101%, respectively, above control levels. The increase in PMN adhesion to PAEC was associated with a threefold increase in endothelial cell-associated platelet-activating factor (PAF) compared with control PAEC. The conditioned media from PAEC exposed to hypoxia also contained sixfold more PAF than control conditioned media, and it activated PMN to become adherent to untreated PAEC. The hypoxia-induced PAEC adhesion response was inhibited by preincubating PMN with the specific PAF receptor antagonist, L-659,989. We conclude that PAF is produced by cultured endothelial cells in response to hypoxia and that PAF generation is chiefly responsible for the increased adherence properties of hypoxia-conditioned endothelial cells. This response may play a major role in regulating PMN margination during myocardial ischemia.
Measurement of biventricular septal-to-free wall diameters using sonomicrocrystals
Authors: Yamashita H. , Onodera S. , Morimoto H. , Imamoto T. , Obara A. , Tanazawa S. , Takashio T. , Inoue H. , Omiya H.
Published: December 2017

An ultrasonic system for the measurement of biventricular septal-to-free wall internal diameters in the dog was described. The ventricular endocardial ultrasonic microcrystals were implanted via the left and right atrial appendages and arranged in a straight line, with minimal invasion of the myocardium and pericardium. Reliable signals were obtained during right ventricular pressure overload and septal myocardial ischemia.
Endotoxin enhances arachidonic acid metabolism by cultured rabbit microvascular endothelial cells
Authors: Renzi P. M. , Flynn J. T.
Published: December 2017

This study demonstrates that bacterial lipopolysaccharide and lipid A exert a significant effect on eicosanoid formation by primary cultures of microvascular endothelial cells (MECs). Qualitative studies using [14C]-arachidonic acid demonstrated that prostaglandin E2 was the primary eicosanoid formed by MECs after 20 h of treatment with either vehicle or lipopolysaccharide. Significant, dose-dependent productions of PGE2 and prostacyclin, beginning at an endotoxin dose of 0.01 ng/ml, were quantified by radioimmunoassay in supernatants of cells treated for 20 h with lipopolysaccharide or lipid A. This eicosanoid production was inhibited by meclofenamate and cycloheximide and occurred without cellular injury. The time course and kinetics of eicosanoid production in response to endotoxin demonstrate a significant, time-related enhancement. Endotoxin-treated MECs responded to exogenous substrate with augmented PGE2 production, suggesting enhanced prostaglandin endoperoxide synthase activity. These results demonstrate a significant interaction of endotoxin with endothelial cells of microvascular origin that results in an enhanced potential for eicosanoid metabolism. This effect may be mediated in part through induction of prostaglandin endoperoxide synthase.
Recovery of anoxic-reoxygenated cardiomyocytes from severe Ca2+ overload
Authors: Siegmund B. , Zude R. , Piper H. M.
Published: December 2017

The ability of hypoxic-reoxygenated cardiomyocytes to recover from severe cytosolic Ca2+ overload was investigated using the fluorescent Ca2+ indicator fura-2 in ventricular cardiomyocytes from adult rats. When the fura-2 ratio (340/380 nm) reached saturation in hypoxic cardiomyocytes, indicating severe Ca2+ overload, they were reoxygenated. The cell then suddenly hypercontracted but reestablished, after a phase of Ca2+ oscillations, a normal Ca2+ control. Because these oscillations could be abolished by ryanodine (50 nM), they seem to depend on the function of the sarcoplasmic reticulum (SR). In the presence of caffeine (5 mM) and thapsigargin (100 nM), i.e., agents impairing Ca2+ sequestration in the SR, reoxygenation did not lead to Ca2+ oscillations or to a stable recovery of cytosolic Ca2+ control. The additional presence of ruthenium red (5 microM), an inhibitor of mitochondrial Ca2+ uptake, restored the ability of cells treated with caffeine or thapsigargin to reestablish a normal cytosolic Ca2+ control. The results show that cardiomyocytes are able to recover from severe hypoxic Ca2+ overload if, first, a closed sarcolemma is retained (as in isolated cardiomyocytes) and, second, the SR is available for rapid Ca2+ storage (impaired by caffeine and thapsigargin). The results also suggest that, in the case of an impairment of SR function, the inhibition of mitochondrial Ca2+ uptake (as by ruthenium red) has a protective effect.
The endocardial endothelium
Authors: Brutsaert D. L. , Andries L. J.
Published: December 2017

The heart wall with its complex trabecular structures is covered with a very thin layer of endocardial endothelial (EE) cells. EE cells appear early during cardiac development; they are involved in myocardial trabeculation and the formation of primitive nutrient vessels. This process precedes the development of coronary vessels, Purkinje fibers, and nerve fibers. EE has a different cell shape and cytoskeletal organization than vascular endothelium. The differences in permeability between EE and the coronary vascular endothelium in the subendocardial myocardium might assign characteristic electrochemical properties to the endocardium. Modulation of EE function by substances in the blood constitutes an important intracavitary autoregulation of muscle-pump performance of the heart, i.e., by altering the duration of contraction without significantly altering early contraction dynamics. Such an autoregulation resets the timing of ventricular relaxation and rapid filling with little effect on early systolic contraction and ejection. Both the release by the EE of various substances with inotropic properties and a trans-EE physicochemical control are postulated as possible underlying mechanisms.
Hypoxia-elicited contraction of aorta and coronary artery via removal of endothelium-derived nitric oxide
Authors: Muramatsu M. , Iwama Y. , Shimizu K. , Asano H. , Toki Y. , Miyazaki Y. , Okumura K. , Hashimoto H. , Ito T.
Published: December 2017

To characterize endothelium-derived contracting factor 1 (EDCF1) released under hypoxia, vascular rings isolated from spontaneously hypertensive rat (SHR) aorta and canine coronary artery were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit buffer. In SHR aorta precontracted with norepinephrine (10(-7) M), severe hypoxia induced an initial increase in tension by 36.7 +/- 7.5% followed by a 56.9 +/- 5.7% relaxation; moderate hypoxia induced only a sustained increase in tension by 20.6 +/- 2.5%. Inhibition of nitric oxide (NO) production with N omega-nitro-L-arginine methyl ester (L-NAME) (10(-3) M) augmented norepinephrine-induced precontraction by 76.1 +/- 12.3% and totally eliminated the hypoxic contraction. In canine coronary arteries precontracted with KCl (30 mM) in the presence of indomethacin (10(-5) M), severe hypoxia caused a sustained increase in tension by 68.9 +/- 7.3%, which was also abolished with L-NAME. When L-NAME (10(-3) M) was given after the precontraction, both of these vessels developed sustained contractions under normoxia and moderate hypoxia. These results suggest that the vasocontraction currently considered to be induced by EDCF1 is not caused by a contracting factor but rather is a contracting phenomenon derived from continuous inhibition of basal NO synthesis during hypoxia.
Oxygen radicals in cerebral ischemia
Authors: Nelson C. W. , Wei E. P. , Povlishock J. T. , Kontos H. A. , Moskowitz M. A.
Published: December 2017

Superoxide production was measured as the superoxide dismutase (SOD)-inhibitable portion of nitro blue tetrazolium (NBT) reduction after cerebral ischemia-reperfusion in anesthetized cats equipped with cranial windows. Significant superoxide production was found in the early reperfusion period and continued for more than 1 h after ischemia. Superoxide was not detected in control animals not subjected to ischemia, during ischemia, and at 120 min of reperfusion. After ischemia, the vasoconstrictor response to arterial hypocapnia was reduced. This effect was prevented by pretreatment with SOD plus catalase or by deferoxamine. The response to topical acetylcholine was converted to vasoconstriction after ischemia. The normal vasodilator response reappeared spontaneously at 120 min of reperfusion. The vasodilator response to acetylcholine was preserved in animals pretreated with SOD plus catalase. Blood-brain barrier permeability to labeled albumin and horseradish peroxidase was increased after ischemia. These effects were minimized by pretreatment with SOD and catalase. We conclude that superoxide generation occurs during reperfusion after cerebral ischemia for a fairly long period and that superoxide and its derivatives are responsible at least in part for the vasodilation and the abnormal reactivity as well as for the increase in blood-brain barrier permeability to macromolecules seen after ischemia. Furthermore, the findings suggest that the agent responsible for the vascular abnormalities is hydroxyl radical generated via the iron-catalyzed Haber-Weiss reaction.
Corticoid regulation of atrial natriuretic factor secretion and gene expression
Authors: Dananberg J. , Grekin R. J.
Published: December 2017

This study investigated the acute effects of glucocorticoids and mineralocorticoids on atrial natriuretic factor (ANF) biosynthesis in vivo. Groups of male Sprague-Dawley rats were injected with 1 mg dexamethasone (Dex), 10 mg deoxycorticosterone acetate (DOCA) or vehicle alone. Different groups were studied after periods of 30 min to 8 h. Plasma and left atrial ANF concentrations and ANF mRNA levels were measured 2-8 h after corticoid injection. From 30 min to 2 h after injection, ANF mRNA was analyzed by quantitative and qualitative assessments. There was a two- to threefold increase in plasma levels of ANF in Dex-treated rats compared with controls at all time periods (P < 0.05). Although ANF plasma levels increased over time following DOCA treatment, they were not significantly different from control values. Dex treatment also increased normalized ANF mRNA levels 77% above control levels during the first 4 h after injection (P < 0.05). Thereafter there was a return of mRNA levels to that seen in controls. There was no qualitative difference in the ANF mRNA at any time as assessed by Northern hybridization. In contrast, DOCA increased ANF mRNA levels only after 8 h (P < 0.05). No significant changes in left atrial ANF content were noted during this study. In a separate study, Dex was administered to isolated left atria in vitro in a superfusion system. Superfusion with 2 x 10(-5) M Dex produced a 40% increase in ANF secretory rate within 20 min (P = 0.036). We conclude that Dex induces a direct rapid increase in ANF mRNA levels and ANF secretion in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Physical and physiological characteristics of pressure-driven hemorrhage
Authors: Rocha e Silva M. , Braga G. A. , Prist R. , Velasco I. T. , Franca E. S.
Published: December 2017

Research on hemorrhage has concentrated on its effects rather than the manner of occurrence. A new experimental method in which the rate of bleeding is a function of prevailing arterial pressure is proposed and described. The effects of standard crystalloid volume expansion and of small volume hypertonic treatment on this protocol are demonstrated. In pressure-driven hemorrhage, survival time and the decay of arterial pressure, cardiac output, oxygen consumption, and base excess are functions of the bleeding rate, but plasma proteins and hematocrits are independent. The decay of arterial pressure is also a complex function of blood volume deficit, but this relation is not dependent on the rate of blood removal. Volume expansion induces a recovery of circulatory function despite enhanced blood loss. A comparison between equiosmolar solutions of hypertonic sodium chloride and acetate shows that acetate produces a smaller pressor (hence less blood loss) but larger blood flow (hence higher O2 availability) effect. The possible importance of the isochloremic nature of the response to acetate is highlighted.
Magnitude of beta-adrenoceptor-mediated responses of dog epicardial coronary arteries: inverse relation to diameter
Authors: Krauss S. L. , Dodge J. T. , Bevan J. A.
Published: December 2017

Regional blood flow patterns vary within myocardium to suggest that intrinsic regional differences occur in vasoregulation. Accordingly, we used standard in vitro methodology (isometric force transducer) to study adrenergic responses in epicardial left anterior descending (LAD) artery and right coronary arteries (RCA) obtained from dogs (n = 9). In the presence of propranolol (10(-6) M) and blockers of uptake 1 and 2, norepinephrine (NE) elicited minimal, if any, constriction. After preincubation with phentolamine (10(-6) M) and preconstriction with prostaglandin (PG)F2 alpha or a thromboxane (Tx)A2 analogue, maximum NE relaxation (as % of induced tone) for the RCA was 61 +/- 3 (SE) %, which was significantly greater than the LAD (46 +/- 5%, P < 0.01). ED50 values were not different. Endothelial removal and forskolin relaxations did not change the sensitivity or maximal response between arteries. Expressing beta-adrenoceptor-mediated relaxation as a function of vessel diameter revealed a common regression for RCA and LAD (r = -0.56, P < 0.001). ED50 and diameter were minimally related. Thus the RCA has a greater beta-adrenoceptor response than the LAD in dogs. The difference appears to be reconciled by a common inverse relationship between vessel size and beta-adrenoceptor response. The difference was independent of alpha-adrenoceptor, endothelium, and second messenger processing, suggesting a mechanism based on beta-adrenoceptor density.
Characteristics and origin of myogenic response in isolated mesenteric arterioles
Authors: Sun D. , Messina E. J. , Kaley G. , Koller A.
Published: December 2017

Responses to changes in intravascular pressure of isolated rat mesenteric arterioles were investigated under no-flow conditions. First-, second-, third-, and fourth-generation arterioles were isolated and cannulated. Vascular diameters were measured with an image-shearing device and recorded. The arterioles (except for the first-generation vessels) developed spontaneous tone, corresponding to the step increases in intravascular pressure (from 20 to 160 mmHg, by 20-mmHg steps). For example, at 80 mmHg pressure the mean diameters of first-, second-, third-, and fourth-generation vessels were 286.9 +/- 5.0, 203.4 +/- 8.2, 92.5 +/- 4.6, and 35.6 +/- 4.8 microns, respectively; by use of a Ca(2+)-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) and sodium nitroprusside (SNP; 10(-4) M) the passive diameters of these vessels were 295.6 +/- 6.3, 238.4 +/- 11.7, 120.3 +/- 3.7, and 59.4 +/- 3.1 microns, respectively, demonstrating that the degree of pressure-induced constriction increased with the increasing order of generations (3, 14, 24, and 43%, respectively). The vasoactive function of endothelium and vascular smooth muscle was assessed by the responses of arterioles to acetylcholine (ACh; 10(-6) M) and SNP (10(-7) M) before and after removal of the endothelium with air. After removal of the endothelium, dilation to ACh was abolished while dilation to SNP was retained. Removal of the endothelium did not significantly alter the changes in the diameter of arterioles in response to step increases in intravascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Baroreflex regulation of forearm vascular resistance after exercise in hypertensive and normotensive humans
Authors: Cleroux J. , Kouame N. , Nadeau A. , Coulombe D. , Lacourciere Y.
Published: December 2017

The mechanisms underlying the antihypertensive period following a bout of exercise are not well understood. We examined the aftereffects of exercise on the linear relationship between forearm vascular resistance (FVR) and estimated central venous pressure (CVP) during leg raising and lower body negative pressure to determine whether an alteration of the baroreflex control of FVR was associated with the decreased blood pressure. Blood pressure, forearm blood flow (FBF), and estimated CVP were obtained in 13 hypertensive and 9 normotensive subjects evaluated in a randomized crossover fashion after 30 min of cycle ergometer exercise and after a nonexercise control period. In hypertensive subjects, the reduced blood pressure was accompanied by an increased baseline FBF after exercise. This resulted in a downward shift of the FVR-CVP relationship, while the slope was unchanged. In normotensive subjects, blood pressure and baroreflex control of FVR were unaffected by prior exercise. Four of the hypertensive subjects performed an additional study in which forearm skin was vasodilated with local heating to FVR levels similar to those observed after exercise. Results suggested that the aftereffects of exercise could not be attributed to changes in cutaneous blood flow. We speculate that modulation of the baroreflex control of FVR after exercise contributes to its antihypertensive effect.
Recovery of vascular tissue contractile function during sustained endotoxin exposure
Authors: McKenna T. M.
Published: December 2017

Rat aortic rings incubated in vitro with endotoxin (10 ng/ml, 24 h) exhibited marked suppressions of sensitivity and maximum contraction to norepinephrine as well as a significant increase in guanosine 3',5'-cyclic monophosphate (cGMP) levels. Increasing the incubation time to 42 h did not result in greater suppression; instead, these rings showed improved contractile performance and control-level cGMP. Rings incubated with endotoxin for 18 h and then allowed to recuperate in control medium for another 24 h exhibited normal maximal contractions and cGMP levels; however, these rings remained less sensitive to norepinephrine. An endotoxin-neutralizing protein (50 ng/ml) shielded rings from endotoxin-induced contractile suppression if present during incubation but was unable to restore tissue sensitivity to normal levels if present during the 24-h recuperation. These findings show that vascular tissue exposed to endotoxin has a varied and time-dependent ability to counter the effects of endotoxin on contractile function and intracellular cGMP.