bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans
Authors: Pump Bettina , Damgaard Morten , Gabrielsen Anders , Bie Peter , Christensen Niels Juel , Norsk Peter
Published: December 2017

During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing in eight healthy males, we tested the hypothesis that with similar increases in LA diameter, suppression of AVP release is dependent on the degree of increase in PP. LA diameter increased similarly during the posture change and negative pressure breathing (−9 to −24 mmHg) from between 30 and 31 ± 1 to 34 ± 1 mm ( P < 0.05). The increase in PP from 38 ± 2 to 44 ± 2 mmHg ( P < 0.05) was sustained during the posture change but only increased during the initial 5 min of negative pressure breathing from 36 ± 3 to 42 ± 3 mmHg ( P < 0.05). Aortic transmural pressure decreased during the posture change and increased during negative pressure breathing. Plasma AVP was suppressed to a lower value during the posture change (from 1.5 ± 0.3 to 1.2 ± 0.2 pg/ml, P < 0.05) than during negative pressure breathing (from 1.5 ± 0.3 to 1.4 ± 0.3 pg/ml). Plasma norepinephrine was decreased similarly during the posture change and negative pressure breathing compared with seated control. In conclusion, the results are in compliance with the hypothesis that during maneuvers with similar cardiac distension, suppression of AVP release is dependent on the increase in PP and, furthermore, probably unaffected by static aortic baroreceptor stimulation.
Vitamin C and quinapril abrogate LVH and endothelial dysfunction in aortic-banded guinea pigs
Authors: Bell John P. , Mosfer Salah I. , Lang Derek , Donaldson Francis , Lewis Malcolm J.
Published: December 2017

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG II), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α) levels, and coronary microvascular endothelial cell (CMEC) NAD(P)H-dependent superoxide (O[Formula: see text]) production, and a significant decrease in basal and stimulated CMEC cGMP levels. Treatment of aortic-banded animals with the angiotensin-converting enzyme inhibitor quinapril and the antioxidant vitamin C, either alone or in combination, did not affect BP but caused a significant inhibition of the increases in the heart-to-body weight ratio, ANG II, ET-1, and TNF-α levels, and O[Formula: see text] production and restored cGMP responses to levels comparable with sham-operated animals. These data suggest that quinapril and vitamin C are capable of inhibiting LVH development due to pressure overload via mechanisms that involve the inhibition of oxidative stress, an improvement in coronary endothelial function, and increased nitric oxide bioavailability.
Testosterone relaxes coronary arteries by opening the large-conductance, calcium-activated potassium channel
Authors: Deenadayalu Viju P. , White Richard E. , Stallone John N. , Gao Xumei , Garcia Alfredo J.
Published: December 2017

Cardiovascular diseases are often considered to be a predominantly male health problem, and it has been suggested that testosterone exerts deleterious effects on cardiovascular function; however, few experimental studies support this suggestion. Moreover, the cellular and molecular mechanism(s) underlying vascular responses to testosterone is unknown. The present study has investigated the acute effects of testosterone on porcine coronary artery smooth muscle at the tissue and cellular levels. Contractile studies demonstrated that testosterone or dihydrotestosterone (a nonaromatizable metabolite) relaxed these arteries by an endothelium-independent mechanism involving potassium efflux. Direct evidence from patch-clamp studies confirmed that testosterone opened K+ channels in single coronary myocytes, and further analysis identified this protein as the large-conductance, calcium- and voltage-activated potassium (BKCa) channel. Moreover, inhibiting BKCachannel activity significantly attenuated testosterone-induced coronary relaxation. These findings indicate that testosterone relaxes porcine coronary arteries predominantly by opening BKCa channels in coronary myocytes, and this response may be associated with accumulation of cGMP. This novel mechanism may provide a better understanding of testosterone-induced vasorelaxation reported in recent experimental and early clinical studies.
Effects of dynamic exercise on mean blood velocity and muscle interstitial metabolite responses in humans
Authors: Lott Mary E. J. , Hogeman Cynthia S. , Vickery Lisa , Kunselman Allen R. , Sinoway Lawrence I. , MacLean David A.
Published: December 2017

We examined the effects of dynamic one-legged knee extension exercise on mean blood velocity (MBV) and muscle interstitial metabolite concentrations in healthy young subjects ( n = 7). Femoral MBV (Doppler), mean arterial pressure (MAP) and muscle interstitial metabolite (adenosine, lactate, phosphate, K+, pH, and H+; by microdialysis) concentrations were measured during 5 min of exercise at 30 and 60% of maximal work capacity (Wmax). MAP increased ( P < 0.05) to a similar extent during the two exercise bouts, whereas the increase in MBV was greater ( P < 0.05) during exercise at 60% (77.00 ± 6.77 cm/s) compared with 30% Wmax (43.71 ± 3.71 cm/s). The increase in interstitial adenosine from rest to exercise was greater ( P < 0.05) during the 60% (0.80 ± 0.10 μM) compared with the 30% Wmax bout (0.57 ± 0.10 μM). During exercise at 60% Wmax, interstitial K+ rose at a greater rate than during exercise at 30% Wmax ( P < 0.05). However, pH increased (H+ decreased) at similar rates for the two exercise intensities. During exercise, interstitial lactate and phosphate increased ( P < 0.05) with no difference observed between the two intensities. After 5 min of recovery, MBV decreased to baseline levels after exercise at 30% Wmax (4.12 ± 1.10 cm/s), whereas MBV remained above baseline levels after exercise at 60% Wmax (Δ19.46 ± 2.61 cm/s; P < 0.05). MAP and interstitial adenosine, K+, pH, and H+ returned toward baseline levels. However, interstitial lactate and phosphate continued to increase during the recovery period. Thus an increase in exercise intensity resulted in concomitant changes in MBV and muscle interstitial adenosine and K+, whereas similar changes were not observed for MAP or muscle interstitial pH, lactate, or phosphate. These data suggest that K+ and/or adenosine may play an active role in the regulation of skeletal muscle blood flow during exercise.
eNOS 894T allele and coronary blood flow at rest and during adenosine-induced hyperemia
Authors: Naber Christoph K. , Baumgart Dietrich , Altmann Christoph , Siffert Winfried , Erbel Raimund , Heusch Gerd
Published: December 2017

The 894T allele of a G894T polymorphism in the endothelial nitric oxide synthase ( eNOS) gene is associated with decreased eNOS activity, cleavage of the protein, and endothelial dysfunction. The present study evaluated the association with coronary blood flow (CBF) at rest and during adenosine (ADO)-induced hyperemia. CBF was determined by Doppler flow wire and angiography in 97 left anterior descending arteries of individuals without coronary artery disease. At rest, average peak velocity (APV) was lower and coronary vascular resistance (CVR) was higher in homozygous carriers of the 894T allele than in heterozygotes and individuals without the 894T allele. CBF tended to be lower in eNOS 894T allele carriers. During ADO-induced hyperemia (18 μg ic), APV, CVR, and CBF were not statistically different between the genotypes. The reduced APV at rest in conjunction with an increased CVR indicates a vasomotor dysfunction related to an increased microvascular resting tone in eNOS 894T allele carriers.
Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 μm
Authors: Versluis J. Pieter , Heslinga Johannes W. , Sipkema Pieter , Westerhof Nico
Published: December 2017

Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (Pint). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, Pint were calculated with nonlinear regression. The Pint at the level of the septal artery (diameter, 150–250 μm) was 23.2 ± 4.4 cmH2O ( n = 12). In arterioles with a diameter range between 24 and 110 μm, Pint was 1.7 ± 0.5 cmH2O ( n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, Pint was 1.1 ± 1.1 cmH2O ( n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 μm. The second waterfall is probably located in the small postcapillary venules.
Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin
Authors: Tjen-A-Looi S. C. , Phan N. T. , Longhurst J. C.
Published: December 2017

A number of studies have demonstrated an important role for nitric oxide (NO) in central and peripheral neural modulation of sympathetic activity. To assess the interaction and integrative effects of NO release and sympathetic reflex actions, we investigated the influence of inhibition of NO on cardiac-cardiovascular reflexes. In anesthetized, sinoaortic-denervated and vagotomized cats, transient reflex increases in arterial blood pressure (BP) were induced by application of bradykinin (BK, 0.1–10 μg/ml) to the epicardial surface of the heart. The nonspecific NO synthase (NOS) inhibitor N G-monomethyl-l-arginine (l-NMMA, 10 mg/kg iv) was then administered and stimulation was repeated. l-NMMA increased baseline mean arterial pressure (MAP) from 129 ± 8 to 152 ± 9 mmHg and enhanced the change in MAP in response to BK from 32 ± 3 to 39 ± 5 mmHg ( n = 9, P < 0.05). Pulse pressure was significantly enhanced during the reflex response from 6 ± 4 to 27 ± 6 mmHg after l-NMMA injection due to relatively greater potentiation of the rise in systolic BP. Both the increase in baseline BP and the enhanced pressor reflex were reversed by l-arginine (30 mg/kg iv). Because l-NMMA can inhibit both brain and endothelial NOS, the effects of 7-nitroindazole (7-NI, 25 mg/kg ip), a selective brain NOS inhibitor, on the BK-induced cardiac-cardiovascular pressor reflex also were examined. In contrast to l-NMMA, we observed significant reduction of the pressor response to BK from 37 ± 5 to 18 ± 3 mmHg 30 min after the administration of 7-NI ( n = 9, P < 0.05), an effect that was reversed by l-arginine (300 mg/kg iv, n = 7). In a vehicle control group for 7-NI (10 ml of peanut oil ip), the pressor response to BK remained unchanged ( n = 6, P > 0.05). In conclusion, neuronal NOS facilitates, whereas endothelial NOS modulates, the excitatory cardiovascular reflex elicited by chemical stimulation of sympathetic cardiac afferents.
Overexpression of Na+/Ca2+exchanger alters contractility and SR Ca2+content in adult rat myocytes
Authors: Zhang Xue-Qian , Song Jianliang , Rothblum Lawrence I. , Lun Mingyue , Wang Xujun , Ding Fan , Dunn Jeremy , Lytton Jonathan , McDermott Paul J. , Cheung Joseph Y.
Published: December 2017

The functional consequences of overexpression of rat heart Na+/Ca2+exchanger (NCX1) were investigated in adult rat myocytes in primary culture. When maintained under continued electrical field stimulation conditions, cultured adult rat myocytes retained normal contractile function compared with freshly isolated myocytes for at least 48 h. Infection of myocytes by adenovirus expressing green fluorescent protein (GFP) resulted in >95% infection as ascertained by GFP fluorescence, but contraction amplitude at 6-, 24-, and 48-h postinfection was not affected. When they were examined 48 h after infection, myocytes infected by adenovirus expressing both GFP and NCX1 had similar cell sizes but exhibited significantly altered contraction amplitudes and intracellular Ca2+concentration ([Ca2+]i) transients, and lower resting and diastolic [Ca2+]iwhen compared with myocytes infected by the adenovirus expressing GFP alone. The effects of NCX1 overexpression on sarcoplasmic reticulum (SR) Ca2+content depended on extracellular Ca2+concentration ([Ca2+]o), with a decrease at low [Ca2+]oand an increase at high [Ca2+]o.The half-times for [Ca2+]itransient decline were similar, suggesting little to no changes in SR Ca2+-ATPase activity. Western blots demonstrated a significant ( P ≤ 0.02) threefold increase in NCX1 but no changes in SR Ca2+-ATPase and calsequestrin abundance in myocytes 48 h after infection by adenovirus expressing both GFP and NCX1 compared with those infected by adenovirus expressing GFP alone. We conclude that overexpression of NCX1 in adult rat myocytes incubated at high [Ca2+]oresulted in enhanced Ca2+influx via reverse NCX1 function, as evidenced by greater SR Ca2+content, larger twitch, and [Ca2+]itransient amplitudes. Forward NCX1 function was also increased, as indicated by lower resting and diastolic [Ca2+]i.
Initial and sustained phases of myogenic response of rat mesenteric small arteries
Authors: Chlopicki S. , Nilsson H. , Mulvany M. J.
Published: December 2017

A possible role for a metabolite of cytochrome P-450 ω-hydroxylase in the initial and sustained phases of the myogenic response in cannulated rat mesenteric small arteries was studied. With slight preconstriction (norepinephrine and neuropeptide Y), pressure was raised from 60 to 100 mmHg, and both initial (within 2 min) and sustained phases (at 10 min) of the myogenic response were quantified. The myogenic response was fully inhibited by D600 (methoxyverapamil). Ketoconazole and 17-octadecanoic acid did not affect the initial phase but inhibited the sustained phase. In contrast, miconazole did not affect either phase. Charybdotoxin and iberiotoxin potentiated the initial phase but eliminated the sustained phase. Apamin, glibenclamide, 4-aminopyridine, and barium had no effect on either phase. The results demonstrate different mechanisms for the initial and sustained phases of the myogenic response of rat mesenteric small arteries. Only the sustained phase appears mediated through a cytochrome P-450 ω-hydroxylase metabolite and calcium-activated K+ channels. However, both phases of the response are dependent on calcium influx through voltage-dependent calcium channels.
Antisense inhibition of Na+/Ca2+exchange during anoxia/reoxygenation in ventricular myocytes
Authors: Eigel B. N. , Hadley R. W.
Published: December 2017

This study investigated the role of the Na+/Ca2+exchanger (NCX) in regulating cytosolic intracellular Ca2+concentration ([Ca2+]i) during anoxia/reoxygenation in guinea pig ventricular myocytes. The hypothesis that the NCX is the predominant mechanism mediating [Ca2+]ioverload in this model was tested through inhibition of NCX expression by an antisense oligonucleotide. Immunocytochemistry revealed that this antisense oligonucleotide, directed at the area around the start site of the guinea pig NCX1, specifically reduced NCX expression in cultured adult myocytes by 90 ± 4%. Antisense treatment inhibited evoked NCX activity by 94 ± 3% and decreased the rise in [Ca2+]iduring anoxia/reoxygenation by 95 ± 3%. These data suggest that NCX is the predominant mechanism mediating Ca2+overload during anoxia/reoxygenation in guinea-pig ventricular myocytes.
Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO·
Authors: Dai Lijun , Brookes Paul S. , Darley-Usmar Victor M. , Anderson Peter G.
Published: December 2017

A rat aortic banding model of cardiac hypertrophy was used to test the hypothesis that reversible inhibition of mitochondrial respiration by nitric oxide (NO·) elicits a bioenergetic defect in the hypertrophied heart. In support of this hypothesis, the respiration of myocytes isolated from hypertrophied hearts was more sensitive to exogenous NO· (IC50200 ± 10 nM vs. 290 ± 30 nM in controls, P = 0.0064). Hypertrophied myocytes also exhibited significantly elevated inducible NO· synthase (iNOS). Consistent with this endogenous source for NO·, the respiration of hypertrophied myocytes was significantly inhibited at physiological O2tensions versus controls. Both the nonspecific NOS inhibitor nitro-l-arginine and the iNOS-specific inhibitor N-[3-(aminomethyl)- benzyl]acetamidine · 2HCl reversed this inhibition, with no effect on respiration of control myocytes. Consistent with an NO·-mediated mitochondrial dysfunction, the ability of intact perfused hearts to respond to a pacing workload was impaired in hypertrophy, and this effect was reversed by NOS inhibition. We conclude that endogenously generated NO· can modulate mitochondrial function in the hypertrophied heart and suggest that this bioenergetic defect may underlie certain pathological features of hypertrophy.
Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats
Authors: Rakusan Karel , Cicutti N. , Kolar F.
Published: December 2017

The effect of polycythemia on the coronary microcirculation was studied in young male rats. Two experimental models of polycythemia were employed: cobalt-induced polycythemia, which mimics hypoxia-induced changes, and erythropoietin-induced polycythemia, which circumvents these changes. In both models, baseline left ventricular function was normal, whereas maximal systolic and developed pressures were decreased. In cobalt-treated rats the left ventricular functional reserve was also compromised. Morphometric analysis of the left ventricle confirmed previously described improved geometric conditions for oxygen supply at the distal portions of capillaries (smaller domain areas and shorter capillary segments). In cobalt-treated but not in erythropoietin-treated rats, increased capillary angiogenesis was also detected. In the hearts from rats with both types of polycythemia, a small but significant increase in the formation of arterioles was found. Capillary linear hematocrit was within the normal range in both types of polycythemia despite sizeable increases in systemic hematocrit. Significant differences in red blood cell distribution within capillaries were found between proximal and distal portions in all experimental groups.
Interleukin-1β alters brown adipose tissue but not renal sympathetic nerve responses to hypothermia
Authors: Kenney Michael J. , Blecha Frank , Morgan Donald A. , Fels Richard J.
Published: December 2017

Proinflammatory cytokines and acute physical stress influence sympathetic nerve discharge (SND). Because interleukin-1β (IL-1β) produces physiological responses that require central neural integration and because the sympathetic nervous system mediates physiological responses to environmental stress, we hypothesized that IL-1β modulates SND responses to acute physical stress. Therefore, this study examined the effects of IL-1β (290 ng/kg iv) and mild hypothermia on renal and interscapular brown adipose tissue (IBAT) SND regulation in chloralose-anesthetized rats. IBAT SND did not change after IL-1β administration but was significantly increased during acute mild hypothermia, which was induced 60 min after IL-1β treatment. Renal SND was unchanged after IL-1β administration and during hypothermia. Acute hypothermia, without prior IL-1β administration, did not alter IBAT and renal SND. Increases in IBAT SND during sustained (120 min) hypothermia were significantly higher in IL-1β-treated rats compared with saline-treated rats, whereas renal SND responses to sustained hypothermia did not differ among groups. Exposure to acute cold stress after sustained hypothermia produced greater increases in IBAT SND in IL-1β-treated rats compared with saline-treated controls. These data suggest that IL-1β alters IBAT SND responses to acute and sustained hypothermia.
Differential effects of overexpression of two forms of ephrin-A5 on neonatal rat cardiomyocytes
Authors: Li Yun You , Mi Zhibao , Feng Yiqin , McTiernan Charles F. , Zhou Renping , Robbins Paul D. , Watkins Simon C. , Feldman Arthur M.
Published: December 2017

Eph receptors constitute the largest family of receptor tyrosine kinases. Multiple transcripts of ephrin-A5, the cognate ligand of the EphA3 receptor, were found in neonatal rat cardiomyocytes. Two cDNA clones encoding the full-length ephrin-A5 (ephrin-A5α) and a 27-amino acid deletion form (ephrin-A5β) were isolated. To examine the role of ephrin-A5 in cardiomyocytes, the cDNAs were inserted into adenoviral vectors, termed Ad.ephrin-A5α and Ad.ephrin-A5β, respectively, and overexpressed in cardiomyocytes. The effect of ephrin-A5 on cardiomyocyte gene expression was investigated using a cDNA expression array and Western blot analysis. The results showed that both ephrin-A5α and ephrin-A5β downregulated cyclin D2, cyclin-dependent kinase-4 proteins, and their cognate receptor EphA3, which were associated with reduced bromodeoxyuridine incorporation in cardiomyocytes. Whereas ephrin-A5α and ephrin-A5β also induced differential gene expression, only ephrin-A5β significantly upregulated the transcription of brain natriuretic peptide and downregulated ras-related protein RAB2, protein kinase C inhibitor protein-1, clusterin, and insulin-like growth factor-binding protein. The results suggest that the two forms of ephrin-A5 share similar function while differ in regulating different sets of genes in cardiomyocytes.
Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats
Authors: Abe Takehisa , Ohga Yoshimi , Tabayashi Nobuoki , Kobayashi Shuichi , Sakata Susumu , Misawa Hiromi , Tsuji Tsuyoshi , Kohzuki Hisaharu , Suga Hiroyuki , Taniguchi Shigeki , Takaki Miyako
Published: December 2017

To gain insight into the pathogenesis of diabetic cardiomyopathy, we investigated cardiac function in terms of the coupling of left ventricular mechanical work and the energetics in Otsuka Long-Evans Tokushima Fatty rats, which are well known as a model of type 2 diabetes mellitus (DM). Neither left ventricular systolic function and mean coronary flow nor coronary flow reserve differed even in late DM rats. The amount of oxygen required for mechanical work and contraction was unaltered, although myosin isozyme was finally transformed from V1 to V3. The maximum pacing rate was decreased from 300 to 240 beats/min, and the left ventricular relaxation rate was significantly ( P < 0.05) slower only in late DM rats, resulting in decreased oxygen consumption per minute for total Ca2+ handling in excitation-contraction coupling mainly consumed by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) without significant changes in basal metabolism or in mitochondrial oxidative phosphorylation. The protein level of SERCA2 in membranes was significantly ( P < 0.001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats.
Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy
Authors: Piech A. , Massart P. E. , Dessy C. , Feron O. , Havaux X. , Morel N. , Vanoverschelde J.-L. , Donckier J. , Balligand J.-L.
Published: December 2017

Because nitric oxide (NO) regulates cardiac and vessel contraction, we compared the expression and activity of the endothelial NO synthase (eNOS) and caveolin, which tonically inhibits eNOS in normal and hypertrophic cardiomyopathic hearts. NOS activity (l-[3H]citrulline formation), eNOS immunostaining, and caveolin abundance were measured in heart tissue of 23 mongrel dogs before and at 3 and 7 wk of perinephritic hypertension (PHT). Hemodynamic parameters in vivo and endothelial NO-dependent relaxation of macro- and coronary microvessels in vitro were assessed in the same animals. eNOS immunostaining and total calcium-dependent NOS activity decreased at 7 wk in all four heart cavities (in left ventricle, from 17.0 ± 1.3 to 0.2 ± 0.2 fmol · min−1 · mg protein−1, P < 0.001). Caveolin-1 and -3 also decreased in PHT dog hearts. Accordingly, basal vascular tone was preserved, but maximal endothelial NO-dependent relaxation was impaired in all vessels from 7-wk PHT dogs. The latter had preserved systolic function but impaired diastolic relaxation [relaxation time constant ( T 1), 25.1 ± 0.9 vs. 22.0 ± 1 ms in controls; P < 0.05]. Peripheral infusion of the NOS inhibitor N G -nitro-l-arginine methyl ester increased mean aortic pressure in both groups and reduced diastolic ( T 1, 31.9 ± 1.4 ms) and systolic function in PHT dogs (DP40, 47.5 ± 2.5 vs. 59.4 ± 3.8 s−1 in control animals). In conclusion, both eNOS and caveolin proteins are decreased in the hypertrophic hearts of PHT dogs. This is associated with altered maximal (but not basal) vascular relaxation and impaired diastolic function. Further degradation of cardiac function after NOS inhibition suggests a critical role of residual NOS activity, probably supported by the concurrent downregulation of caveolin.
Role of CO in attenuated vasoconstrictor reactivity of mesenteric resistance arteries after chronic hypoxia
Authors: Gonzales Rayna J. , Walker Benjimen R.
Published: December 2017

Chronic hypoxia (CH) is associated with a persistent reduction in systemic vasoconstrictor reactivity. Experiments on aortic ring segments isolated from CH rats suggest that enhanced vascular expression of heme oxygenase (HO) and resultant production of the vasodilator carbon monoxide (CO) may underlie this attenuated vasoreactivity after hypoxia. Similar to the aorta, small arteries from CH rats exhibit blunted reactivity; however, the regulatory role of CO in the resistance vasculature has not been established. Therefore, we examined the significance of HO activity on responsiveness to phenylephrine (PE) in the mesenteric circulation of control and CH rats. To document that the mesenteric bed demonstrates reduced reactivity after CH, we determined the vasoconstrictor responses of conscious, chronically instrumented male Sprague-Dawley rats to PE under control conditions and then immediately after exposure to 48 h CH (0.5 atm). All rats showed reduced mesenteric vasoconstriction to PE after CH. To examine the role of CO in reduced reactivity, small mesenteric arteries (100–200 μm intraluminal diameter) from control and 48-h CH rats were isolated and mounted on glass cannulas, pressurized to 60 mmHg and superfused with increasing concentrations of PE under normoxic conditions. Similar to the intact circulation, vessels from CH rats exhibited reduced vasoconstrictor sensitivity to PE compared with controls that persisted in the presence of nitric oxide synthase inhibition. The HO inhibitor, zinc protoporphyrin IX (5 μM) enhanced reactivity only in CH vessels. Additionally, a range of concentrations of the HO substrate heme-l-lysinate caused vasodilation in CH vessels but not in controls. Thus we conclude that CO contributes a significant vasodilator influence in resistance vessels after CH that may account for diminished vasoconstrictor responsiveness under these conditions.
Comparison of the vascular effects of adenosine in isolated mouse heart and aorta
Authors: Talukder M. A. Hassan , Morrison R. Ray , Mustafa S. Jamal
Published: December 2017

The present study was designed to characterize and compare the vascular effects of adenosine and its analogs in the murine heart and aorta. Mouse hearts perfused under constant pressure in standard Langendorff fashion demonstrated concentration-dependent increases in coronary flow to adenosine, 2-chloradenosine (CAD), 5′-( N-ethyl-carboxamido)-adenosine (NECA), and 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxam-idoadenosine (CGS-21680). All agonists produced comparable increases in coronary flow with the following order of potency: CGS-21680 = NECA ≫ CAD ≥ adenosine. In l-phenylephrine hydrochloride (phenylephrine) precontracted aortic rings, all nonselective agonists (NECA, CAD, and adenosine) produced marked concentration-dependent relaxation, whereas the adenosine A2Aselective agonist CGS-21680 did not. Adenosine receptor agonists were >100 times more potent for coronary vasodilation than aortic vasorelaxation. The selective A2Areceptor antagonist 5-amino-7-(β-phenylethyl)-2-(8-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidine (SCH-58261) blocked both CGS-21680- and NECA-induced increases in coronary flow, whereas the A2Breceptor antagonist benzo[g]pteridine-2,4(1H,3H)-dione (alloxazine) inhibited NECA-induced aortic relaxation. These data indicate a differential response to adenosine agonists in murine coronary vasculature and aorta where coronary vasodilation is mediated predominantly by activation of A2Aadenosine receptors.
Alterations of endothelium-dependent and -independent regulation of coronary blood flow during heart failure
Authors: Saito Tomiyoshi , Maehara Kazuhira , Tamagawa Kazuaki , Oikawa Yuji , Niitsuma Takeo , Saitoh Shu-Ichi , Maruyama Yukio
Published: December 2017

Conflicting data concerning the changes in basal coronary blood flow and nitric oxide (NO)-releasing capacity in chronic heart failure may be due to different phases or duration of heart failure. To investigate endothelium-dependent and -independent regulation of coronary blood flow in different phases of heart failure, coronary pressure-flow relationships during long diastole were obtained before and after rapid pacing of 3 and 5 wk at 240 beats/min in 12 or 6 dogs. Neither basal coronary blood flow nor the slope of coronary pressure-flow relationships changed; however, zero-flow pressure increased slightly after rapid pacing. Intracoronary injection of N G-nitro-l-arginine methyl ester decreased coronary blood flow at a perfusion pressure of 50 mmHg by ∼20% at baseline, 55% after 3 wk of rapid pacing, and 20% after 5 wk of rapid pacing. Acetylcholine-induced increase in coronary blood flow was maintained for 3 wk but was finally attenuated after 5 wk of rapid pacing. In contrast, the coronary blood flow response to adenosine gradually decreased with time. These results suggest that basal coronary blood flow is maintained until the late stage of heart failure, presumably by an increases in NO production during the early stage and then by other vasodilatory substances during the late stage, and that endothelium-dependent vasodilation via exogenously administered acetylcholine in resistance vessels is not necessarily impaired in the early stage despite the gradual reduction of endothelium-independent vasodilation via adenosine in chronic heart failure.
Renin in the kidneys of rats with aminonucleoside nephrosis
Authors: Gross F. , Buschor O. , Zeugin P.
Published: December 2017

An experimental nephrotic syndrome was produced in rats by aminonucleoside administration. Unlike previous results in animals given excess mineralocorticoid, aminonucleoside did not reduce the renin content of the kidney; did not cause an increased sensitivity to single or repeated doses of renin, whether renin was given from the beginning of the experiment or 2 days before edema formation; and did not cause hypertension. The severity of the nephrotic syndrome was augmented by a high-salt diet. The syndrome could be produced in adrenalectomized animals on maintenance doses of desoxycorticosterone acetate, suggesting that the hyperaldosteronism of aminonucleoside nephrosis is not the cause of the observed edema and ascites. Sharp distinctions can be drawn between the mechanisms of edema formation in experimental nephrosis and those of the ‘eclampsia-like’ syndrome.
Effect of Pitressin on old-age changes of salt and water metabolism in the rat
Authors: Friedman Sydney M. , Friedman Constance L. , Nakashima Miyoshi
Published: December 2017

Extracellular fluid volume is characteristically increased in old rats. This is accompanied by a parallel increase in extracellular Na but not K. Daily urine volume and, to a lesser degree, daily urinary Na excretion is also increased in old rats even in the presence of severe water deprivation. These changes, together with an increase in adrenal size, are similar to those observed in diabetes insipidus in the rat. Daily treatment with Pitressin tannate, tested at only one dose level, tended to restore the relevant values towards those of younger normals.
Carbonate fixation in the lactating beagle dog
Authors: Luick Jack R. , Black Arthur L. , Parker Harold R.
Published: December 2017

A study has been made of the importance of carbonate fixation in the synthesis of milk by the lactating beagle dog. C14-labeled biocarbonate, injected intravenously, was used as a tracer of these processes. Approximately 90% of the injected C14 appeared in the expired CO2 by 3 hours after the injection. Milk lactose was 3.5 times more radioactive than casein; very little activity was found in the milk fat. Carbonate fixation accounted for 5.3% of lactose C, 1.6% of casein C, and 0.6% of fat C. These values are 50% lower than those found earlier for the cow. This difference was found to be consistent with accepted concepts of ruminant and nonruminant metabolism.
Electrical activity of the entorhinal cortex during conditioned behavior
Authors: Holmes J. E. , Adey W. R.
Published: December 2017

A 4–6-cps wave form was observed in the entorhinal cortex of 8 out of 10 cats studied with the implanted electrode technique. When the animals were trained to approach a concealed food reward, the slow waves always accompanied the act of walking to the goal, and the rhythm stabilized in the range of 5–6 cps. When the habit was subjected to extinction, the rhythm gradually dropped out, to return promptly with retraining. Stimulation of the entorhinal area had no effect on behavior as long as seizures were avoided. A similar 6–6-cps rhythm was observed in the hippocampus during the early stages of training in two animals. It is suggested that the entorhinal slow waves are a correlate of an alert state of readiness to act.
Influence of diet on transamidinase activity in dystrophic mice
Authors: Coleman D. L. , Ashworth M. E.
Published: December 2017

The activities of the enzymes involved in creatine synthesis were studied in normal and dystrophic mice maintained on two commercial mouse chows. Kidney transamidinase activity in the dystrophic mouse was found to vary from 150 to –50% of the normal depending on the diet fed while the activity of the enzyme in the control mice remained unaltered. Addition of protein or glycine to the diet normally causing the lower transamidinase values resulted in increased enzyme levels equal to those found in animals maintained on the diet normally producing the higher enzyme levels.
Direct measurement of blood pressures in minute vessels of the liver
Authors: Nakata K. , Leong G. F. , Brauer R. W.
Published: December 2017

A method has been described which allows the insertion of microneedles into minute blood vessels of the transilluminated rat liver. Using dye injections under controlled pressures and direct observation, blood pressures in the terminal portal venules as well as in the central veins of this preparation have been determined and have been compared with simultaneous pressure measurements in the mesenteric veins and in the vena cava at the level of entry of the hepatic veins. The results indicate an unexpectedly large pressure drop in the portal venous tree (from 13 cm H2O in the portal vein to approximately 6 cm in the portal venules), a significant pressure drop between portal venules and central veins (from 6 to 2.5 cm H2O), and a paradoxical mean pressure relation between central vein and vena cava. Discussion of these results has been presented in terms of methodological problems, the implication of the results for the control of blood flow distribution in the liver, and the intermittency of hepatic vein flow in the rat.
Effect of intravenous phospholipid and Triton on lipids of normal and ethanol-treated rats
Authors: Di Luzio N. R. , Zilversmit D. B.
Published: December 2017

The administration of ethanol to normal rats results in a significant increase in liver neutral fat. The continuous intravenous administration of either choline or soya lecithin following ethanol administration did not modify the development of the fatty liver. However, the infusion of soya lecithin significantly increased plasma cholesterol levels in both normal and ethanol-treated rats. In normal rats the continuous intravenous infusion of soya lecithin was associated with a pronounced elevation in free cholesterol and a decrease in the esterified fraction. The latter alteration was not observed when egg lecithin was employed. Injection of nonionic detergents did not reproduce the plasma or liver lipid response evoked by phospholipids.
Renal excretion of creatinine in the rat
Authors: Glasser Lewis
Published: December 2017

The exogenous creatinine clearance was measured in rats using a technique of constant intravenous infusion, and was compared with simultaneous measurement of the radioinulin clearance. Creatinine/inulin clearance ratios were significantly higher than unity at plasma concentrations of creatinine less than 150 mg%, indicating tubular secretion of creatinine. At higher plasma creatinine concentrations (150–500 mg%) the clearance ratios were depressed and did not differ significantly from one. It is concluded that at higher plasma creatinine concentrations the exogenous creatinine clearance may be used as an estimate of glomerular filtration rate.
Salivary responses to cortical and sciatic stimulation
Authors: Velo A. G. , Hoff E. C.
Published: December 2017

In cats under ether and Flaxedil, submandibular salivation in response to electrical stimulation of the central cut end of the sciatic nerve and cortical loci on sigmoid gyrus and gyrus proreus has been evoked. These responses were obtained in animals with solely sympathetic or parasympathetic innervation of the gland intact. The ascending path in the cord (for parasympathetic and sympathetic effects) runs in the dorsal part of the lateral funiculus. In acute animals, the relay for both effects takes place somewhere between the upper cervical level of the spinal cord and the midcollicular level of the brainstem. A segmental activation of sympathetic salivary responses may have been masked by autonomic spinal shock. The excitable cortical area overlaps those yielding vasomotor responses, adrenal medullary activity and bladder contractions. The descending pathway for sympathetic effects runs in the spinal cord (at the cervical level) at the junction of the dorsal and ventral parts of the lateral funiculus, a region also containing descending vasomotor fibers.
Effect of digitalis on active intestinal sugar transport
Authors: Csaky T. Z. , Hartzog H. G. , Fernald G. W.
Published: December 2017

Ouabain (10–6 moles) and thevetin (10–7 moles) completely inhibit the active transport of 3-methylglucose across the intestine of the frog in vitro. Acetylstrophanthidin has a weak inhibitory action. The results are discussed in view of a possible link between active ionic and sugar transport mechanisms.
Accumulation of L-phenylalanine by segments of small intestine
Authors: Samiy A. H. , Spencer Richard P.
Published: December 2017

Segments of hamster small intestine accumulate l-phenylalanine from an in vitro solution without degradation of the amino acid. Uptake by the segments equilibrates in about 20 minutes, while transport of the amino acid across intestinal sacs requires nearly 1 hour. This suggests that the initial event preceding transintestinal transport is cellular uptake of l-phenylalanine. Concentration of the amino acid in the wall of intestinal sacs during l-phenylalanine transport was equal to or greater than that in the serosal fluid. Hence it is possible that intramural accumulation is the active process and outward diffusion from wall to serosa is the passive event. Dependence of segmental uptake of l-phenylalanine on external concentration, and its increased magnitude in midintestinal segments, resembles the process occurring in intestinal sacs. On the basis of the time course of events, concentration within the wall, and concentration and site dependence, it is proposed that intestinal uptake of l-phenylalanine is the initial and essential event in its transport. For l-phenylalanine uptake, the KM calculated from initial rate data was identical to that found from equilibrium data. Usefulness of intestinal segment uptake in determining initial rates and other parameters is pointed out.
Effect of 10% oxygen on electrocardiogram of the atherosclerotic rabbit
Authors: Winbury Martin M. , Wolf Joanne K. , Cronin M. T. I.
Published: December 2017

Dutch belted rabbits, on a 2% cholesterol diet for periods up to 300 days, were periodically subjected to anoxia (10% O2) tests. During the control diet period no electrocardiographic changes were produced by the anoxia test. After 2 1/2 months on cholesterol some of the animals showed an S-T segment depression during the anoxia test. This positive anoxia response was observed in 87% of the animals after 4 1/2 months on the cholesterol diet. A comparison of the anoxia test with the ergonovine test (50 µg/mg) was made. Many of the animals with a positive anoxia response were negative with ergonovine. Nitroglycerine, 5–40 mg/kg i.v., or aminophylline, 10 mg/kg i.v., did not prevent the S-T segment depression produced by the anoxia test. Three animals were returned to the control diet after 5 months on the cholesterol diet; the positive anoxia response persisted for another 3 months but was absent after 5 months on the control diet. However, there was no regression of aortic or coronary plaques. Gross and microscopic observations demonstrated marked atherosclerotic changes in the aorta, pulmonary artery and coronary arteries in all cholesterol-fed animals. There was aortic stenosis and the cusps of the aortic and mitral valves were rigid. In addition, there was evidence of myocardial damage.
Some factors affecting the vago-vagal reflex
Authors: Mohamed A. H. , Bakhoum W. , Zaki O. , Zaki K. , Yowakim S.
Published: December 2017

The purpose of this investigation was to examine the effect on duration of vagal asystole caused by changing the oxygen and carbon dioxide content of arterial blood. The pH of blood was determined in every experiment. It was proved that, in control animals, the duration of vagal asystole varied from dog to dog, but it was constant in each animal receiving repeated stimulation under the same conditions. A decrease in O2 content or an increase in CO2 content of arterial blood, or both, produced a longer period of asystole. The possible mechanisms are discussed.
Dimensional and dynamic features of mammalian gastrocnemius muscle
Authors: Thomson J. D.
Published: December 2017

Attempts were made to determine how behavior of the separate heads of the rat gastrocnemius muscle are related to give responses characteristic of the whole muscle. The lateral head is heavier and shows greater isometric twitch tension than the medial head; the sum of the twitch tensions approximates values for whole muscle. Isometric tetanus tensions of the two heads are of equal magnitude; their sum is only 68% of the value for whole muscle, the deficit being due to loss of mechanical advantage by being separated. Maximum rates of isometric twitch and tetanus tension development and decay are slower in the medial than in the lateral head. The sum of the rates of twitch development approximates the value for whole muscle; the sum of rates of tetanic tension development is 65% of the value for whole muscle, this deficit also being due to loss of mechanical advantage. The medial head has a longer latent period and twitch contraction time and a greater degree of twitch fusion than the lateral head. Load-velocity curves of separate heads are similar and resemble the responses of two halves of a single muscle split lengthwise.
Circulatory performance under surgical stress during adrenocortical suppression
Authors: Papacostas Charles A.
Published: December 2017

In dogs, the oral administration of prednisolone phosphate at 50 mg/day for 14 days did not induce significant adrenocortical suppression as evidenced by a pronounced elevation in plasma free 17-hydroxycorticosteroid (17-OHCS) after surgical trauma. In another group the same drug regimen caused a failure of steroid elevation when a rapid functional ACTH test was performed. A minor degree of adrenocortical inhibition probably occurred. In this circumstance, the difference in adrenocortical responses may have been related to the more prolonged and therefore effective stimulation of the adrenal cortex by surgery. The same dose of prednisolone given for a 28-day period induced failure of any adrenocortical response to surgical stress. Despite a definitely limited adrenocortical reserve, the animals withstood surgery and a 2-day postoperative period with no evidence of circulatory collapse or impairment of the pressor response to levarterenol. The findings pose a question as to the significance of high levels of plasma 17-OHCS normally observed under stress, beyond providing a minimal quantity necessary for homeostasis.
Separation of cardioaccelerator and coronary vasomotor fibers in the dog
Authors: Juhasz-Nagy A. , Szentivanyi M.
Published: December 2017

Page 125: A. Juhász-Nagy and M. Szentiványi, "Separation of cardioaccelerator and coronary vasomotor fibers in the dog." Page 127, second column, second sentence should read: While the A-V O2 difference and the lactate difference increased proportionately in response to preganglionic stimulation, during postganglionic stimulation the A-V lactate difference increased, decreased, or was unchanged, depending on the prevalence of enhanced release, increased uptake, or a balanced uptake and output of lactate.
Motility of the gastric fundus
Authors: Lind James F. , Duthie Herbert L. , Schlegel Jerry F. , Code Charles F.
Published: December 2017

This study was undertaken to define the motor activity of the fundus of the stomach. Observations were made on six healthy dogs with vagally innervated mucosal septal pouches of the fundus of the stomach and four other healthy dogs with identical pouches of the corpus of the stomach. In each dog the motor actions of the esophagus, gastroesophageal sphincter, gastric pouch, and gastric antrum were recorded simultaneously. The commonest motor activity recorded from the pouches of the fundus was a slow, phasic change in pressure or tone designated as a type III wave. Tiny pressure changes occurring at a rate of 5/min and identical to type I waves seen elsewhere in the stomach were sometimes recorded. Large "fundic" waves, occurring, when they were rhythmic, at a rate of about 3/min were occasionally seen on the records. Relaxation of the pouch of the fundus occurred after the majority of swallows, confirming the observation of other investigators that receptive relaxation of the fundus is an important component of the response to deglutition.