bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of vasopressin on left ventricular performance
Authors: Cheng C. P. , Igarashi Y. , Klopfenstein H. S. , Applegate R. J. , Shihabi Z. , Little W. C.
Published: December 2017

We assessed the effect of arginine vasopressin (AVP) on left ventricular (LV) performance in eight conscious dogs. Five minutes after AVP infusion (6 microns.kg-1 x min-1 for 2 min) the plasma AVP was elevated from 3.9 +/- 0.9 to 14.7 +/- 4.6 pg/ml (P < 0.05). With all reflexes intact, AVP caused significant increases in LV end-systolic pressure (P) (112 +/- 8 vs. 122 +/- 7 mmHg, P < 0.05) end-systolic volume (V) (30 +/- 5.8 vs. 38 +/- 7.7 ml, P < 0.05), total systemic resistance (6.2 +/- 1.8 vs. 10.6 +/- 4.0 mmHg.dl-1 x min, P < 0.01) and arterial elastance (Ea) (6.8 +/- 3.0 vs. 8.6 +/- 3.9 mmHg/ml, P < 0.05), while the heart rate (110 +/- 6 vs. 82 +/- 10 beats/min, P < 0.05) and stroke volume (16.5 +/- 4.3 vs. 14.2 +/- 3.9 ml, P < 0.05) were decreased. There was no significant change in the coronary sinus blood flow (82 +/- 19 vs. 78 +/- 22 ml/min, P = not significant). AVP decreased the slopes of LV end-systolic P-V relation (10.7 +/- 1.1 vs. 8.1 +/- 1.9 mmHg/ml, P < 0.05), the maximal first derivative of LV pressure (dP/dtmax)-end-diastolic volume (VED) relation (135.2 +/- 18.7 vs. 63.1 +/- 7.7 mmHg.s-1 x ml-1, P < 0.05), and the stroke work-VED relation (81.1 +/- 4.1 vs. 66.7 +/- 2.8 mmHg, P < 0.05) and shifted the relations to the right, indicating a depression of LV performance. A similar increase in Ea produced by methoxamine did not depress LV performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha-adrenergic modulation of transient outward current in hyperthyroid rabbit myocytes
Authors: Shimoni Y. , Banno H.
Published: December 2017

The alpha 1-adrenergic modulation of the transient outward potassium current (I(t)) was studied in single cardiac myocytes obtained from normal (euthyroid) and hyperthyroid rabbits. Rabbits were made hyperthyroid by four or five daily intraperitoneal injections of 0.4 mg/kg body wt thyroxine. Currents were recorded using the whole cell, suction-electrode, voltage-clamp method. It was found that the alpha-adrenergic agonist methoxamine attenuates I(t) in rabbit ventricular cells, as reported earlier for atrial cells. This attenuation is significantly reduced in the hyperthyroid state. For example, 0.2 mM reduces I(t) magnitude (at +20 mV) by close to 40% in euthyroid cells and by only 20% in the hyperthyroid cells. Half-maximal effective concentration values (extrapolated) are close to 0.4 mM in normal and 1 mM in hyperthyroid cells. Preliminary results show similar effects in atrial cells as well. These results may be related to a decrease in the density of membrane alpha-adrenergic receptors in hyperthyroid conditions, or to the induction of a new class of I(t) channels that is less sensitive to alpha-agonists.
Effect of captopril on sympathetic preganglionic efferent activity in cats
Authors: Montano N. , Gnecchi-Ruscone T. , Contini M. , Finocchiaro M. L. , Lombardi F. , Malliani A.
Published: December 2017

In 13 decerebrate cats, we studied the effects of captopril (10 mg/kg iv bolus) on the background discharge of thoracic preganglionic sympathetic fibers. After drug administration there was an initial reduction in systolic arterial pressure (SAP), which was followed by a later inhibition of sympathetic discharge (from 2.7 +/- 0.5 to 0.79 +/- 0.1 imp/0.1 s; P < 0.01). Captopril significantly reduced the excitatory response of sympathetic fibers to premature ventricular contraction (70 +/- 17 vs. 257 +/- 30%), inferior vena cava obstruction (176 +/- 56 vs. 315 +/- 85%) and asphyxia (143 +/- 20 vs. 245 +/- 51%). Vice versa the sympathetic response to aortic occlusion was unaffected (-58 +/- 8 vs. -62 +/- 6%). A similar reduction in sympathetic discharge was observed after captopril administration in anesthetized cats (n = 3). On the contrary, no changes in background neural discharge were noticed in decerebrate-spinalized cats (n = 5), despite comparable hemodynamic effects. These data indicate that captopril reduces sympathetic efferent activity and its responsiveness to excitatory stimuli. The lack of neural effects in decerebrate-spinalized cats is consistent with a brain stem site of action of captopril.
Effect of limb anesthesia on middle cerebral response to handgrip
Authors: Jorgensen L. G. , Perko G. , Payne G. , Secher N. H.
Published: December 2017

Transcranial Doppler ultrasound was used to measure middle cerebral arterial mean flow velocity (Vmean) on both sides of the brain in 12 subjects during hand contractions before and during regional anesthesia of the left arm. At rest Vmean was 49 (36-104) cm/s (median and range) and was unaffected by regional anesthesia. During right-hand contractions Vmean remained unchanged on the right side of the brain, whereas it increased 20 (4-37)% (P < 0.01) on the left side of the brain. Similarly, during left-hand contractions Vmean increased 24 (2-42)% (P < 0.01) on the right side of the brain, while it remained unchanged on the left side of the brain. Regional anesthesia did not quantitatively affect Vmean during right-hand contractions. In contrast, during left-hand contractions, both right and left Vmean tended to decrease. Increases in Vmean appeared despite a decrease in arterial carbon dioxide tension (P < 0.01). Heart rate and blood pressure responses to hand contractions were enhanced during regional anesthesia (P < 0.01), but left-hand contractions resulted in a less pronounced increase in blood pressure (P < 0.01). These data demonstrate a contralateral increase in cerebral perfusion during hand contractions that is dependent on intact afferent input from the working limb.
Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to catecholamines in septic rats
Authors: Hollenberg S. M. , Cunnion R. E. , Zimmerberg J.
Published: December 2017

Induction of nitric oxide synthase by cytokines has been hypothesized as a mechanism of the hyporesponsiveness to catecholamines that occurs in clinical septic shock. We measured responses of resistance arterioles in rat cremaster muscle to topically suffused norepinephrine in vivo with the use of image-shearing videomicroscopy. Rats made septic by cecal ligation and puncture were compared with controls that underwent sham ligation. The norepinephrine concentration-response curve was shifted to the right in septic rats [50% effective concentration (EC50) 9.1 +/- 5.4 vs. 0.10 +/- 0.02 microM, P < 0.05]. Contractions at doses of 10(-9), 10(-8), and 10(-7) M norepinephrine were 26, 41, and 38%, respectively, of sham controls. Superfusion of the muscle with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine at 100 microM restored the arteriolar responsiveness of the septic rats (EC50 0.14 +/- 0.07 vs. 6.8 +/- 3.1 microM, P < 0.05). This effect was reversed with superfusion of excess (1 mM) L-arginine. These experiments demonstrate impaired vasoconstriction in response to norepinephrine in resistance arterioles of septic rats in vivo. NG-monomethyl-L-arginine reversed this hyporesponsiveness, implying that nitric oxide synthase may mediate the decreased catecholamine responsiveness associated with sepsis.
Impaired early and intact late diastolic function in stunned myocardium induced by demand ischemia
Authors: Miyazaki S. , Goto Y. , Nonogi H. , Kawase Y. , Haze K. , Hiramori K.
Published: December 2017

Changes in left ventricular diastolic properties of pacing-induced stunned myocardium were examined in 10 anesthetized dogs instrumented with a micromanometer for left ventricular pressure and sonomicrometers for left ventricular short axis, anterior and posterior segment lengths, and posterior wall thickness. After the creation of a critical stenosis on a carotid-circumflex coronary artery bypass, left ventricular pressure and dimensions were recorded simultaneously during temporary superior and inferior vena caval occlusion to allow for the construction of end-diastolic pressure-segment length curves. After 15 min of high-frequency pacing (190–220 beats/min), measurements were repeated and compared with those before pacing. The mean lengthening rate of each dimension during the first half of diastole was calculated as an index of early diastolic function. Three minutes after the end of pacing, coronary blood flow and perfusion pressure were unchanged, whereas systolic function of the posterior wall was depressed, indicating stunning of the posterior myocardium. The time constant of left ventricular pressure decay was prolonged by 14%. The mean lengthening rate during the first half of diastole decreased by 50% in the left ventricular internal short axis and by 119% in the posterior segment. Despite the significant impairment of early diastolic function, the regional end-diastolic pressure-segment length relation of the posterior wall was unchanged. Thus, in contrast to the results reported for pacing-induced ischemia that were measured immediately after pacing, the distensibility of the left ventricular wall in stunned myocardium induced by pacing was unchanged despite depressed early diastolic function.
Effects of cocaine on sarcoplasmic reticulum in skinned rat heart muscle
Authors: Tomita F. , Bassett A. L. , Myerburg R. J. , Kimura S.
Published: December 2017

We examined the effects of cocaine on the ability of the sarcoplasmic reticulum (SR) to release and accumulate Ca2+ and on the Ca2+ sensitivity of the contractile proteins using chemically skinned rat left ventricular muscles. The preparations were treated with saponin (40 micrograms/ml for Ca2+ release and uptake studies and 200 micrograms/ml for Ca(2+)-tension experiments). The SR was loaded with 10(-6) M Ca2+ solution; SR Ca2+ release was induced by application of 5 or 25 mM caffeine. The amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. After 1 min of SR Ca2+ loading, simultaneous application of 50 microM cocaine and 5 mM caffeine increased caffeine-induced Ca2+ release by 15.7 +/- 3.1% (P < 0.05). However, when Ca(2+)-loaded preparations were treated with cocaine for 1 min before application of 5 mM caffeine, caffeine-induced Ca2+ release was reduced by 17.1 +/- 3.0% (P < 0.05). When cocaine was applied during the Ca2+ loading periods, the amount of Ca2+ accumulated by the SR (the area under the 25 mM caffeine-induced contraction) increased for both 1-min (10.9 +/- 1.7%, P < 0.05) and 3-min (15.5 +/- 4.4%, P < 0.05) Ca2+ loading periods. Cocaine (50 microM) had no effect on the Ca2+ sensitivity of the contractile system. We conclude that cocaine at a concentration of 50 microM can directly alter the ability of the SR to release and accumulate Ca2+. These effects of cocaine, especially those on SR Ca2+ release, may play a role in its potential for induction of cardiac toxicity.
Myocardial blood flow and VO2 in lambs with an aortopulmonary shunt during strenuous exercise
Authors: Gratama J. W. , Meuzelaar J. J. , Dalinghaus M. , Koers J. H. , Gerding A. M. , Monchen M. T. , te Nijenhuis F. C. , Zijlstra W. G. , Kuipers J. R.
Published: December 2017

To determine how much myocardial O2 consumption (VO2) would increase during an additional load on the heart in shunt as compared with control lambs, we studied 12 7-wk-old lambs with an aortopulmonary left-to-right shunt (59 +/- 3% of left ventricular output, mean +/- SE) and 11 control lambs during exercise at 80% of their predetermined peak VO2 (VO2peak), at 12 +/- 1 days after surgery. During exercise, systolic aortic pressure increased by 25% in the two groups. Left atrial pressure and left ventricular stroke volume did not change significantly and remained considerably higher in shunt than in control lambs. Heart rate, however, increased less in shunt than in control lambs (163 +/- 8 to 235 +/- 8 vs. 107 +/- 7 to 230 +/- 8 beats/min). The same was true for left ventricular myocardial blood flow (245 +/- 19 to 391 +/- 27 vs. 128 +/- 10 to 320 +/- 45 ml.min-1 x 100 g-1) and myocardial VO2 (847 +/- 101 to 1,692 +/- 136 vs. 528 +/- 58 to 1,579 +/- 178 mumol O2 x min-1 x 100 g-1). We conclude that, despite the volume load, myocardial VO2 of shunt lambs does not increase to a greater extent than in control lambs during a considerable additional load on the heart.
Role of Na(+)-Ca2+ exchange in the regulation of vascular smooth muscle tension
Authors: Motley E. D. , Paul R. J. , Matlib M. A.
Published: December 2017

To determine the role of the Na(+)-Ca2+ exchange systems of nerve terminal and sarcolemmal membrane on development of tension in rabbit aortic rings, internal or external Na+ concentration was changed with either ouabain or Na(+)-free solution, respectively. Ouabain produced a verapamil-insensitive but external Na(+)- and Ca(2+)-dependent biphasic tension with distinct lag periods both of which were shortened by depolarization with KCl. The first phase of tension was inhibited by prazosin, phentolamine, in vitro neurolysis with 6-hydroxydopamine and in vivo treatment with reserpine to deplete catecholamines in nerve terminals. Therefore, first phase of tension was attributed to catecholamines released from nerve terminals induced by increased axoplasmic Ca2+ concentration mediated by the neural Na(+)-Ca2+ exchanger due to the increased axoplasmic Na+ concentration resulting from inhibition of the Na(+)-Ka+ pump with ouabain. In the absence of the first phase of tension, the second phase of tension was enhanced by caffeine, presumably by preventing sequestration of the sarcolemmal Na(+)-Ca2+ exchanger-mediated increase in cytosolic Ca2+ concentration in vascular smooth muscle cells. The prazosin-insensitive tension was dependent on the external Na+ concentration and was also attributed to the sarcolemmal Na(+)-Ca2+ exchanger of vascular smooth muscle. The magnitude of the increase in tension with ouabain or Na(+)-free solution attributed to the sarcolemmal Na(+)-Ca2+ exchanger of vascular smooth muscle was larger than that mediated by the exchanger of the nerve terminal. It was concluded that the Na(+)-Ca2+ exchange systems of both the nerve terminal and the vascular smooth muscle sarcolemma contribute to the development of tension by different mechanisms and to different extents when internal or external Na+ concentration was changed.
Acute resetting of the carotid sinus baroreflex by aortic depressor nerve stimulation
Authors: Hayward L. , Hay M. , Felder R. B.
Published: December 2017

The effect of prolonged aortic depressor nerve (ADN) stimulation on carotid sinus baroreflex regulation of arterial pressure (AP) and renal sympathetic nerve activity (RSNA) was examined in anesthetized rabbits. Ramp increases in carotid sinus pressure (CSP) were repeated before and after 5 min of bilateral ADN stimulation. One minute after ADN stimulation the curve relating AP to CSP had shifted up and to the right, characterized by significant increases (P < 0.05) in the maximum (91 +/- 2 to 101 +/- 3 mmHg; mean +/- SE), midpoint (118 +/- 7 to 125 +/- 8 mmHg CSP), and minimum (45 +/- 3 to 53 +/- 4 mmHg) of the AP reflex curve. There was a parallel shift downward of the curve relating RSNA to CSP, characterized by significant decreases in the maximum [100 +/- 0 to 66 +/- 8% of maximum control RSNA value (%max)], the range (90 +/- 2 to 59 +/- 8%max), and the gain (-1.0 +/- 0.2 to -0.5 +/- 0.1%max/mmHg) of the RSNA reflex curve. Values returned to control within 10 min of cessation of ADN stimulation. These results suggest that central neurons processing baroreflex information from one set of mechanoreceptors can be reset by convergent signals arising from another baroreceptor site.
Comparison of conduit vessel and resistance vessel reactivity: influence of intimal permeability
Authors: Matsuki T. , Hynes M. R. , Duling B. R.
Published: December 2017

Arterioles of hamster cheek pouches are less reactive to luminal application of small hydrophilic agents than to adventitial application. To explore possible longitudinal variations in response sidedness, we compared reactivity of isolated vessels from carotid arteries to first-order arterioles. Concentration-response curves for luminally or adventitially applied phenylephrine (PE) were constructed. Arterioles were 274-fold less responsive when PE was in luminal vs. adventitial responsiveness decreased as vessel diameters increased, from 24-fold in inferior saccular arteries to 18-fold in external maxillary arteries and, finally, to 3-fold in common carotid arteries. Differences in response to luminal or adventitial application of PE could be eliminated in arterioles by perfusion with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), which disrupts membrane integrity. Treatment with CHAPS also increased the transmural movement of sodium fluorescein across arteriolar vessel walls. We conclude that a diffusion barrier exists in arterial walls, that there is a longitudinal variation in this barrier as expressed by the differences in movement of small hydrophilic molecules from lumen to smooth muscle cell layers, and that the site of the barrier is likely to be at the endothelial cell membrane.
Depletion and refilling of intracellular Ca2+ stores induce oscillations of Ca2+ current
Authors: Vaca L. , Kunze D. L.
Published: December 2017

An agonist-induced Ca2+ influx pathway in vascular endothelium and other nonexcitable cells is closely aligned with the depletion of microsomal Ca2+ stores. The mechanism by which this occurs is unknown. In these studies 2',5',-di(tert-butyl-1,4-benzohydroquinone, a specific inhibitor of the microsomal Ca(2+)-adenosinetriphosphatase, and patch-clamp recordings were used to evaluate the relationship of inward Ca2+ current to the depletion of intracellular Ca2+ stores. The results demonstrate that depletion and refilling of Ca2+ stores control the amplitude of an electrogenic influx pathway in vascular endothelium. Prominent fluctuations in Ca2+ current occur when there is an imbalance between depletion and refilling of the stores. Furthermore, the studies suggest that the Ca2+ influx pathway is spatially in close association with the intracellular store.
Differential action of plasma and albumin on transcapillary exchange of anionic solute
Authors: Huxley V. H. , Curry F. E. , Powers M. R. , Thipakorn B.
Published: December 2017

We tested two hypotheses to account for the reduction in coupling of anionic solute to water flow (solvent drag) in microvessels during perfusion with plasma compared with albumin. Solvent drag is determined by both hydraulic conductivity (Lp) and solute reflection coefficient (sigma). Accordingly, decreased solvent drag during plasma perfusion must be the result of an increase in sigma (hypothesis 1) or reduction of Lp (hypothesis 2) or some combination of both mechanisms. These hypotheses were assessed by measuring Lp, sigma, and diffusive solute permeability (Psd) to the anionic protein alpha-lactalbumin in frog mesenteric exchange microvessels during plasma or albumin perfusion. The solute permeability coefficient to alpha-lactalbumin (Ps alpha-lactalbumin) was lower during exposure to plasma than bovine serum albumin (BSA) [(Ps alpha-lactalbumin)plasma/(Ps alpha-lactalbumin)BSA = 0.31 +/- 0.11 (means +/- SE, n = 9)]. Solute reflection coefficient to alpha-lactalbumin (sigma alpha-lactalbumin) was 0.69 +/- 0.02 in plasma and 0.34 +/- 0.03 in BSA (n = 7). Lp was not significantly influenced by perfusate protein composition (Lp plasma/Lp BSA = 1.02 +/- 0.11; n = 20). These data lead to the conclusion that the actions of plasma are to confer charge selectivity for anionic solute and, to a lesser extent, modify the porous pathways of the microvessel wall. Taken together, these results indicate that porous pathways contribute significantly to macromolecular flux in plasma-perfused vessels.
Effects of acetylcholine on spontaneous contractions in isolated bovine mesenteric lymphatics
Authors: Yokoyama S. , Ohhashi T.
Published: December 2017

The effects of acetylcholine (ACh) on spontaneous contractions in isolated bovine mesenteric lymph vessels were investigated. ACh ranging from 3 x 10(-8) M to 10(-5) M produced dose-dependent negative chronotropic and inotropic effects on the spontaneous contractions. In the lymph vessels without endothelium, ACh at the same concentration range had no significant effect on the spontaneous contractions. Atropine (10(-9) and 10(-8) M) caused a parallel shift to the right of the dose-chronotropic response curve for ACh. The pA2 value of atropine to ACh in the negative chronotropic effect was 8.90 +/- 0.20 (n = 6). Aspirin (10(-5) M) produced no significant inhibition of the ACh-induced negative chronotropic and inotropic effects. NG-monomethyl-L-arginine (L-NMMA; 3 x 10(-5) M) significantly suppressed the ACh-induced negative responses on spontaneous contractions. In the same lymphatic segments, L-arginine (10(-4) M) reversed completely the inhibition by L-NMMA of the ACh-induced responses. These results suggest that low concentrations of ACh produce negative chronotropic and inotropic effects on spontaneous contractions in bovine mesenteric lymphatics and that the responses may be mediated by nitric oxide or its related compound released from the endothelial cells through activation of low-affinity muscarinic receptors.
CaATPase content is lower in cardiac sarcoplasmic reticulum isolated from old rats
Authors: Taffet G. E. , Tate C. A.
Published: December 2017

The rate of oxalate-facilitated ATP-dependent calcium uptake by the calcium pump, calcium adenosinetriphosphatase (CaATPase), is 30-40% slower in the sarcoplasmic reticulum (SR) isolated from the hearts of senescent Fischer 344 male rats. To determine the underlying mechanism, cardiac SR was isolated from 11- to 12-mo-old (adult) and 22- to 24-mo-old (senescent) male Fischer 344 rats. The yield of SR and contamination by other membrane organelles were similar between the groups. The rate of calcium uptake by the homogenate and isolated SR was 28-44% slower (P < 0.05) in the senescent group. In the isolated SR the calculated maximal velocity (Vmax) of CaATPase activity as a function of varying concentrations of ATP or calcium was 20-30% lower (P < 0.05) in the senescent group; however, the affinities for both calcium and ATP of CaATPase activity were unaltered. The lower Vmax was matched by a decreased (P < 0.05) content of calcium-dependent phosphoenzyme (EP) in the SR isolated from the senescent rats. Thus the ratio of enzyme activity to phosphoenzyme content (Vmax/EP) was similar between the groups. The immunoreactive CaATPase protein was 22 +/- 2% lower in the SR from the senescent rats. Taken together the data indicate that the major mechanism underlying the slower calcium transport by cardiac SR isolated from old rats is a lower content of the CaATPase protein.
Microvascular pressure profile of serosal vessels of rat trachea
Authors: Ballard S. T. , Nations R. H. , Taylor A. E.
Published: December 2017

Pages H1303–H1304: S. T. Ballard, R. H. Nations, and A. E. Taylor. “Microvascular pressure profile of serosal vessels of rat trachea.” Measurements of microvessel diameter were overestimated because of a calibration error. The corrected vessel diameters are 0.56 times those originally reported. The corrected diameter ranges for arterioles, venules, and venular sinuses should be 6–53, 11–42, and 67–236 μm, respectively. When it is assumed that capillaries fall between 10-μm arterioles and venules, capillary pressures predicted by a four-parameter logistical function range from 34.5 and 12.7% of mean arterial pressure. Therefore, when the average large venular pressure was 5% of mean arterial pressure, fractional precapillary (systemic to 10-μm-diam arterioles), capillary (10-μm-diam arterioles to 10-μm-diam venules), and postcapillary (10-μm-diam venules to large venules) resistances would represent 69, 23, and 8%, respectively, of the total microvascular resistance. A revised Fig. 1 comparing experimental data with those of Nordin et al. (3), who measured microvascular pressure in rabbit tracheal mucosa, follows.

(See PDF)
Effect of dietary salt on arteriolar nitric oxide in striated muscle of normotensive rats
Authors: Boegehold M. A.
Published: December 2017

This study evaluated the influence of high dietary salt intake on nitric oxide (NO) activity in the arteriolar network of rats resistant to salt-induced hypertension. The spinotrapezius muscle microvasculature was studied in inbred Dahl salt-resistant (SR/Jr) rats fed low (0.45%)- or high (7%)-salt diets for 4–5 wk. Arterial pressures were not different between groups at any time during the study. NO synthesis inhibition with NG-nitro-L-arginine-methyl ester (L-NAME) constricted arcade arterioles in low-salt SR/Jr and dilated arcade arterioles in high-salt SR/Jr. Arcade arteriole dilation to acetylcholine (ACh), but not sodium nitroprusside (SNP), was impaired in high-salt SR/Jr. In contrast, transverse and distal arteriole responses to L-NAME, ACh, and SNP were identical in high- and low-salt SR/Jr. These findings indicate that high salt intake, in the absence of increased arterial pressure, suppresses the influence of basal and evoked NO on vascular tone in arcading arterioles, but not in smaller transverse and distal arterioles. Unaltered SNP responses in high-salt SR/Jr suggest that this effect does not involve a change in arteriolar smooth muscle responsiveness to NO.
Pericardial mechanoreceptors with phrenic afferents
Authors: Kostreva D. R. , Pontus S. P.
Published: December 2017

Pericardial mechanoreceptors with afferents in the phrenic nerves were studied in anesthetized dogs. The specific aims determined 1) if pericardial receptors with phrenic afferents exist in the dog; 2) the stimuli needed to activate these receptors; 3) the anatomic distribution of these pericardial receptors; and 4) which pericardial layer contains the receptors. Afferent activity was recorded from the phrenic nerves while the pericardium was probed. In 15 of 18 animals, pericardial receptors were found on the right side. In 12 of 18 animals pericardial receptors were located on the left side. Most of the mechanoreceptors were found in a band that paralleled the pericardiophrenic attachment, in the fibrous layer of the pericardium, overlying the atria and atrioventricular grooves. Some receptors had a cardiac rhythm, whereas others were stimulated by the inflating lung. None of the receptors were chemosensitive to capsaicin, bradykinin, or saline. This study is the first to demonstrate that the pericardium of the dog contains mechanosensitive receptors which are innervated by the phrenic nerve.
Pyruvate and lactate metabolism in the in vivo dog heart
Authors: Laughlin M. R. , Taylor J. , Chesnick A. S. , DeGroot M. , Balaban R. S.
Published: December 2017

Pyruvate increases the phosphorylation potential in perfused heart to a greater extent than the closely correlated substrate L-lactate. Therefore, metabolism of these compounds was studied in the myocardium of intact dogs. Phosphocreatine/ATP was increased 23% at 5.3 mM plasma pyruvate but was not significantly increased by lactate except at the highest concentration (17.5 mM in blood). Calculated [ADP] fell during pyruvate infusion from 51.5 +/- 2.0 to 38.6 +/- 3.3 microM but did not change significantly during lactate infusion. Intracellular free [Mg2+] fell from 705 +/- 53 to 498 +/- 30 microM at the highest pyruvate infusion and from 692 +/- 112 to 417 +/- 19 microM with lactate infusion. Extraction of both substrates was linear at low concentrations, reaching 0.56 mumol lactate.min-1.g wet wt-1 at 17.5 mM blood lactate and 0.58 mumol pyruvate.min-1.g wet wt-1 at 5.3 mM plasma pyruvate. Therefore, lactate uptake was almost five times lower than pyruvate uptake at similar concentrations. Elevated pyruvate (> 3 mM) resulted in almost complete inhibition of net lactate uptake. Infused [3-13C]lactate or -pyruvate gave rise to labeled glutamate and alanine in vivo, but labeled lactate was not visible when [3–13C]pyruvate was the substrate. The 13C enrichment of myocardial lactate was similar to alanine and acetyl CoA with infused [3–13C]lactate but was only one-half that of alanine and acetyl CoA when [3–13C]-pyruvate was the substrate, indicating a possible inhibition of lactate dehydrogenase.
Mechanical stimulation induces intercellular calcium signaling in bovine aortic endothelial cells
Authors: Demer L. L. , Wortham C. M. , Dirksen E. R. , Sanderson M. J.
Published: December 2017

To study the mechanism by which endothelial cells respond to mechanical forces, we used digital fluorescence microscopy to measure changes in intracellular Ca2+ concentration ([Ca2+]i) in primary cultures of bovine aortic endothelial cells in response to mechanical stimulation. Before stimulation, [Ca2+]i was stable (approximately 50–75 nM). When an individual cell within the monolayer was mechanically stimulated with a microprobe, [Ca2+]i increased in the stimulated cell and spread in the form of a wave from the site of contact to the cell edges. After a delay of approximately 1 s, nonstimulated adjacent cells showed a similar spreading rise in [Ca2+]i. This outwardly radiating [Ca2+]i wave involved progressively more distal cells to a radius of 4–6 cells. The time delay before the wave appeared in adjacent cells increased, and peak [Ca2+]i in each cell decreased with distance from the stimulated cell. In the absence of extracellular Ca2+, there was no increase in [Ca2+]i in the stimulated cell, yet a wave of increased [Ca2+]i occurred in neighboring cells as if communicated from the stimulated cell. These results indicate that endothelial cell mechanosensitivity results in increases in [Ca2+]i and that the temporospatial dynamics of intercellular Ca2+ signaling are mediated by a diffusible substance other than Ca2+.
Possible paracrine facilitation of ventricular growth in oculo by atrial tissue
Authors: Love Timothy C. , Tucker Diane C.
Published: December 2017

Pages H1082–H1068: Timothy C. Love and Diane C. Tucker. “Possible paracrine facilitation of ventricular growth in oculo by atrial tissue.” Page H1085: Figure 3 should appear as follows.

(See PDF)
Adenosine stimulates proliferation of human endothelial cells in culture
Authors: Ethier M. F. , Chander V. , Dobson J. G.
Published: December 2017

The effect of adenosine on proliferation of human endothelial cells was investigated by adding adenosine to the medium of cultures derived from human umbilical veins. Cell counts on cultures grown in 10 microM adenosine for 4–7 days were 41–53% greater than counts from control cultures. In contrast, 10 microM adenosine had no effect on growth of a human fibroblast cell strain (IMR-90). Neither inosine nor 2',5'-dideoxyadenosine influenced endothelial cell growth at concentrations of 0.1 or 10 microM. Addition of adenosine deaminase abolished the proliferative effect of added adenosine and inhibited proliferation by 16% in control cultures, suggesting that endogenous adenosine may enhance proliferation in culture. The adenosine receptor antagonist, 8-phenyltheophylline, at 0.1 and 1.0 microM blocked the enhanced proliferation caused by 10 microM adenosine. Addition of 10 microM adenosine enhanced DNA synthesis in endothelial cell cultures as indicated by an increased incorporation of [3H]thymidine into acid-insoluble cell material. The results indicate that addition of physiological concentrations of adenosine to human umbilical vein endothelial cell cultures stimulates proliferation, possibly via a surface receptor, and suggest that adenosine may be a factor for human endothelial cell growth and possibly angiogenesis.
Effects of collagenase, elastase, and hyaluronidase on mechanical properties of isolated dog jugular veins
Authors: Kitoh T. , Kawai Y. , Ohhashi T.
Published: December 2017

To study the contribution of tissue components to the mechanical properties of veins, pressure-volume relationships were obtained with the cylindrical segments of isolated dog external jugular veins at several levels of longitudinal extension. At each length, the transmural pressure of the segment was raised up to 20 cmH2O and then reduced to 0 cmH2O by increasing and decreasing the intraluminal volume at a constant rate. The longitudinal extension of the venous segments caused a significant reduction in the incremental volume elasticity within the pressure range of 0–2 cmH2O (E0-2) as well as a significant increase of the incremental volume elasticity within 10–20 cmH2O (E10-20). The pressure-volume relationships of venous segments were also constructed in the same way after treatment with 1 mg/ml collagenase for 30 min, 0.1 mg/ml elastase for 5 min, or 1 mg/ml hyaluronidase for 60 min. Treatment with collagenase or elastase produced a significant increase of the E0-2. The treatment, however, caused no effect on E10-20. Treatment with hyaluronidase induced no effect on these mechanical parameters but produced a significant attenuation of the extension-induced decrease in E0-2. Activation of the venous smooth muscles induced by norepinephrine (10(-4) M) or high-potassium Krebs solution caused a significant decrease of E0-2 as well as a significant increase of E10-20. A complete relaxation of the smooth muscles elicited by Ca(2+)-free Krebs solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (2 mM) caused an increase of E0-2. Mechanical rubbing of the endothelium caused no significant effect on E0-2 and E10-20.(ABSTRACT TRUNCATED AT 250 WORDS)
Limit to cardiac compensation during acute isovolemic hemodilution: influence of coronary stenosis
Authors: Levy P. S. , Kim S. J. , Eckel P. K. , Chavez R. , Ismail E. F. , Gould S. A. , Ramez Salem M. , Crystal G. J.
Published: December 2017

We assessed limit to cardiac compensation during isovolemic hemodilution (HD) in 14 anesthetized dogs. Radioactive microspheres were used to evaluate myocardial blood flow (MBF) and its transmural distribution (endo/epi). Myocardial O2 consumption (MVO2) and percent lactate extraction were determined. Coronary vasodilator reserve was assessed from reactive hyperemic responses. Dogs were divided into group 1, with intact left anterior descending coronary artery (LAD), and group 2, with critical stenosis of LAD. Measurements were obtained at baseline and during graded HD (Hespan) until cardiac failure (CF). CF occurred at lower hematocrit in group 1 compared with group 2 (9 +/- 1 vs. 17 +/- 1%). In group 1, MBF increased during HD to maintain MVO2 constant; increases in MBF were transmurally uniform until CF, when decreased endo/epi and lactate production suggested subendocardial ischemia. Coronary vasodilator reserve decreased progressively during HD and was absent at CF. In group 2, stenotic LAD demonstrated constant MBF (resulting in decreased MVO2) during HD. At CF, these responses along with reduced endo/epi and lactate production indicated local myocardial ischemia. We conclude that 1) with normal coronary circulation, cardiac function was well maintained over a wide range of hematocrits because increases in MBF were transmurally uniform and sufficient to maintain myocardial oxygenation: CF occurred during extreme HD when MBF became maldistributed, resulting in subendocardial ischemia; 2) critical coronary stenosis impaired coronary vascular adjustment to HD and reduced significantly tolerance of left ventricle to HD; and 3) present findings underscore the importance of recruitment of coronary vasodilator reserve in preserving total and regional myocardial oxygenation during HD.
Collagen characterization in volume-overload- and pressure-overload-induced cardiac hypertrophy in minipigs
Authors: Harper J. , Harper E. , Covell J. W.
Published: December 2017

Previous studies in several different species have shown reduced extractability of collagens in some types of cardiac hypertrophy (volume overload) but not others (pressure overload). The objective of the present study was to examine collagen proteins from the same species (minipigs) with both pressure-overload- and volume-overload-induced cardiac hypertrophy. Hypertrophy was induced by two methods: thoracic banding of the aorta to create pressure overload and arteriovenous shunt to cause volume overload in a porcine model. Collagen types I, III, IV, and V were isolated by pepsin digestion from normal and hypertrophied pig left ventricle tissues. Types I and III collagens from normal and hypertrophied samples, when separated from types IV and V, were digested with cyanogen bromide (CB), and the peptides were examined. Collagen concentration was increased in myocardium removed from hearts subjected to volume overload and unchanged in hearts subjected to pressure overload. The extractability of total collagen was unaffected in pressure-overloaded left ventricles but lower in samples from volume-overloaded hearts. CB digestion cleaved all of the types I and III collagens into similar smaller CB peptides with the exception of a 100-kDa peptide that was observed in both control and hypertrophied hearts. This peptide corresponds to one of the high-molecular-weight peptides found in canine heart tissue. The mature collagen cross-link hydroxylysylpyridinoline (HP) was identified in normal and hypertrophied types I and III collagen from porcine sources. Pressure-overload- and volume-overload-induced cardiac hypertrophy in the pig produced different alterations in the extracellular matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
Biaxial mechanical properties of passive and tetanized canine diaphragm
Authors: Strumpf R. K. , Humphrey J. D. , Yin F. C.
Published: December 2017

The architecture, vascular supply, and ease of tetanization make the diaphragm an ideal structure in which to assess multidimensional mechanical properties of active and passive striated muscle. We developed an isolated, perfused canine diaphragm preparation suitable for the assessment of biaxial stress-strain relations in both the resting state and during tetanization. Each of 33 specimens had a wide, flat region (approximately 3 x 3 cm) wherein there was a single predominant fiber direction. Simultaneous, equal stretchings were imposed in the fiber and perpendicular cross-fiber directions over the same strain ranges in both the passive state and during tetanic contraction. Highly nonlinear behavior was seen in the passive state with a limit of extensibility in both directions. The specimens were also markedly anisotropic, with the cross-fiber direction being stiffer than the fiber direction (slopes of the regression line for the stresses in each direction averaged 3.97). Moreover, 31 of the 33 specimens were stiffer in the cross-fiber direction, one was isotropic, and one was stiffer in the fiber direction. During tetanization, the extent and distribution of anisotropy were significantly altered (regression slope averaged 1.08, and 18 specimens were now either isotropic or stiffer in the fiber direction). Disrupting the membranes covering each surface increased extensibility and decreased the anisotropy, thereby suggesting that these membranes bear most of the passive load and contribute greatly to the cross-fiber stiffness and anisotropy of the intact diaphragm. Both before and after disruption of the surface membranes, there was still a consistent increase in cross-fiber stress during tetanization, implying active force generation perpendicular to the fiber direction.(ABSTRACT TRUNCATED AT 250 WORDS)
Age-related changes in endothelium-dependent hyperpolarization in the rat mesenteric artery
Authors: Fujii K. , Ohmori S. , Tominaga M. , Abe I. , Takata Y. , Ohya Y. , Kobayashi K. , Fujishima M.
Published: December 2017

This study was designed to determine the age-related changes in the endothelium-dependent hyperpolarization to acetylcholine (ACh) and its contribution to relaxation in the isolated mesenteric artery from normotensive and hypertensive rats. Membrane potentials and contractions were recorded in arteries from male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) that were 5-6 wk old (young), 6-8 mo old (adult), and 20-26 mo old (aged). Endothelium-dependent hyperpolarizations produced by ACh, applied both at the resting state of the membrane and under conditions of depolarization with norepinephrine (10(-5) M), were markedly impaired in aged WKY rats, adult SHR, and aged SHR. Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were also impaired in aged WKY rats, adult SHR, and aged SHR even in the presence of indomethacin. Furthermore, in these rats, N omega-nitro-L-arginine, an inhibitor of nitric oxide formation, showed potent inhibitory effects on the relaxations, whereas the 20 mM high K+ solution that reduces hyperpolarization had less pronounced effects. Hyperpolarizations and relaxations to cromakalim (10(-5) M), a K(+)-channel opener, were on the whole preserved in aged rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced with aging as well as by hypertension, and this would, in part, account for the impaired relaxation to ACh in arteries of both aged rats and hypertensive rats.
Neuropeptide Y potentiates contractile response to norepinephrine in skate coronary artery
Authors: Bjenning C. , Holmgren S. , Farrell A. P.
Published: December 2017

The skate is an extant representative of the first vertebrate group with a coronary circulation, the elasmobranch fish. Histochemical studies have revealed that skate coronary arteries are innervated by adrenergic nerves as well as by nerves showing neuropeptide Y (NPY)-like immunoreactivity. This study investigates the effect of NPY in the coronary system of an elasmobranch fish, a vertebrate that first evolved 450 million years before mammals and the mammalian coronary circulation. The responses of vascular ring preparations of the coronary artery from the longnose skate (Raja rhina) were measured using isometric force transducers. The main effect of NPY was a potentiation of the amplitude of the norepinephrine-induced contraction, leaving the pD2 value (-log 50% effective concentration) for norepinephrine unaffected. NPY per se occasionally contracted the coronary rings in higher concentrations. The potentiation response may not involve the endothelium and was abolished by pretreatment with tetrodotoxin. We conclude from this study that NPY potentiates norepinephrine-induced contraction in skate coronary artery via an indirect pathway.
Preconditioning protects coronary arteriolar endothelium from ischemia-reperfusion injury
Authors: DeFily D. V. , Chilian W. M.
Published: December 2017

The objectives of this study were to test the hypotheses that 1) endothelium-dependent regulation of coronary arteriolar reactivity is impaired after ischemia and reperfusion, and 2) preconditioning protects the arteriolar endothelium from reperfusion injury. In anesthetized open-chest dogs, coronary arteriolar diameters (30-110 microns) were measured in the beating heart using intravital microscopy during fluorescent stroboscopic epi-illumination in three groups: 1) control, 2) ischemia and reperfusion: 60-min occlusion and 120-min reperfusion of the left circumflex coronary artery, and 3) preconditioning: 10-min occlusion and reperfusion preceding ischemia-reperfusion. To evaluate endothelial reactivity, the diameter responses of coronary arterioles to the endothelium-dependent vasodilators, acetylcholine and serotonin, were assessed. Ischemia and reperfusion significantly reduced the increase in diameter by serotonin (0 +/- 2 vs. 11 +/- 3% change in controls; P < 0.05) and acetylcholine (7 +/- 2 vs. 20 +/- 2% in controls; P < 0.05). In contrast, preconditioning preserved the dilation to both serotonin (6 +/- 1%) and acetylcholine (24 +/- 3%; both NS vs. control; P < 0.05 vs. ischemia and reperfusion). Dilation by the endothelium-independent vasodilator, papaverine, was similar in the three groups, indicating similar levels of vasodilatory reserve and suggesting that the impaired dilation to acetylcholine and serotonin after ischemia and reperfusion was not due to nonspecific damage to vascular smooth muscle. These data demonstrate that ischemia-reperfusion significantly attenuates endothelium-dependent vasodilation of coronary arterioles in the intact beating heart. Furthermore, preconditioning reduces the endothelial dysfunction of coronary arterioles after ischemia-reperfusion.
Impaired regional subendocardial coronary flow reserve in conscious dogs with pacing-induced heart failure
Authors: Shannon R. P. , Komamura K. , Shen Y. T. , Bishop S. P. , Vatner S. F.
Published: December 2017

The purpose of the present investigation was to examine coronary flow and vasodilator reserve in conscious, chronically instrumented dogs with pacing-induced heart failure, a model of severe biventricular cardiomyopathy devoid of significant hypertrophy. Twelve dogs were studied after 28 days of rapid right ventricular pacing and were compared with six sham-operated controls. Left ventricular (LV) average transmural flow was significantly less in conscious dogs with pacing-induced heart failure, whereas the endocardial-to-epicardial flow ratio was not significantly different. In response to near maximal coronary vasodilation with adenosine, subepicardial coronary flow and vasodilator reserve were preserved in congestive heart failure (CHF), yet there was evidence of impaired subendocardial flow and vasodilator reserve, and the endocardial-to-epicardial ratio was significantly less. When the markedly elevated LV end-diastolic pressure was normalized in heart failure, there was restoration of subendocardial coronary flow reserve and a normalization of the endocardial-to-epicardial ratio. Thus, in CHF, there is impaired coronary flow and vasodilator reserve that is selective to the subendocardium of the LV. At this point in the heart failure process, this impairment is not associated with structural changes but is a consequence of the marked elevation in LV end-diastolic pressure.
Hyperpolarization of in situ rat saphenous vein in response to axial stretch
Authors: Monos E. , Contney S. J. , Dornyei G. , Cowley A. W. , Stekiel W. J.
Published: December 2017

The goal of this study was to measure the effect of axial stretch on vascular smooth muscle (VSM) transmembrane potential (Em) and external diameter (De) of intact and deendothelialized rat saphenous veins (SV). Incremental increases in length of SV were produced in situ by biaxial stretch of its perivascular connective tissue. Em was measured in situ with glass microelectrodes and De with a high-resolution eyepiece or on-line video microangiometer. Vessels were locally denervated by 20 min superfusion with 6-hydroxydopamine. Endothelium was removed by maintaining an air bolus in the lumen for 6 min. Axial stretch of endothelium-intact SV from a baseline length (Lo, at which there was no vessel buckling or folding) to 120% Lo induced a small depolarization from -56 +/- 1.2 to -53 +/- 0.8 mV. This was followed by a substantial hyperpolarization to -65 +/- 1.4 mV at 140% Lo. However, a depolarization was observed in deendothelialized SV from -47 +/- 1.3 mV at Lo to -43 +/- 1.8 mV at 140% Lo. Neither Em response was influenced by local denervation. Relative to Lo, 40% stretch also attenuated norepinephrine-induced vasoconstriction. These results suggest that axial stretch of SV can lead to release of endothelium-derived factor(s) that hyperpolarizes venous VSM and possibly attenuates stretch-induced and adrenergic vasoconstriction. Such a response may act as a protective mechanism to attenuate vasoconstriction induced by axial stretch.