bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic effects of head-down tilt in normal subjects and sustained hypertensive patients
Authors: London G. M. , Levenson J. A. , Safar M. E. , Simon A. C. , Guerin A. P. , Payen D.
Published: December 2017

Central and forearm arterial and venous hemodynamics, arterial baroreflex sensitivity, plasma renin activity, and catecholamines were studied in supine position and after -10 degrees head-down tilt in 29 patients with sustained essential hypertension and in 29 normotensive controls of the same age and sex. In both populations, blood pressure, heart rate, and arterial baroreflex sensitivity did not change during the maneuver. Head-down tilt induced a similar increase in cardiopulmonary blood volume in controls and hypertensives, whereas the increase in central venous pressure, cardiac output, and forearm blood flow was higher in hypertensives. Forearm venous tone decreased in controls (from 16.6 +/- 0.8 to 13.8 +/- 0.9 mmHg X ml-1 X 100 g-1; P less than 0.01) but did not change in hypertensive patients (24.9 +/- 1.6 vs. 25.1 +/- 1.9. The magnitude of forearm vascular resistance changes induced by head-down tilt were significantly related to the basal venous tone in the overall population (P less than 0.01). The decrease in plasma renin activity and plasma catecholamines was similar in the two groups. The study provides the evidence that the higher increase in cardiac output and local flow observed in head-down tilt in hypertensive patients is probably due to a higher change in central venous pressure related to a decrease in venous distensibility.
Centrally induced cardiovascular and sympathetic responses to hydrocortisone in rats
Authors: Takahashi H. , Takeda K. , Ashizawa H. , Inoue A. , Yoneda S. , Yoshimura M. , Ijichi H.
Published: December 2017

Central effects of hydrocortisone were investigated by injecting it intracerebroventricularly (icv) while recording blood pressure and heart rate in awake rats. Dose-dependent increases in both blood pressure and heart rate occurred following injections of hydrocortisone. Pretreatment by icv injections of the angiotensin II antagonist, [Sar1-Ile8]angiotensin II, completely abolished vasopressor responses to subsequent injections of hydrocortisone. When rats were later anesthetized with urethan to allow recording of abdominal sympathetic nerve activity, hydrocortisone produced vasopressor responses accompanied by corresponding increases in sympathetic nerve firing, which were also abolished by central pretreatment with either [Sar1-Ile8]angiotensin II or angiotensin I converting-enzyme inhibitor, captopril. These results indicate that centrally administered hydrocortisone stimulates the brain renin-angiotensin system to produce vasopressor responses by increasing sympathetic nerve firing.
Quantitation of rhythmic diameter changes in arterial microcirculation
Authors: Colantuoni A. , Bertuglia S. , Intaglietta M.
Published: December 2017

The diameter of the arterial and arteriolar blood vessels was measured as a function of time in the hamster skin fold window preparation. When the animals recovered from the surgical implantation, the diameters of the arterial microvessels exhibited a continuous rhythmic activity throughout the preparation for a period of 2 wk while the chamber was intact. The amplitude of the diameter changes was directly proportional to the mean vessel size. The frequency of this phenomenon was determined by power spectrum analysis implemented with a Fourier transform method and was found to decrease from a maximum of 9-15 cycles/min in 8- to 15-micron A4 arterioles to 1-3 cycles/min in 70- to 100-micron A1 small arteries. A1 and A4 vessels had relatively well-defined characteristic fundamental frequencies, whereas A2 and A3 vessels showed a power spectrum that included the frequencies present in A1 and A4 vessels. The activity was not synchronized throughout the microvasculature, and frequencies and amplitudes of diameter variations changed at branching points. Anesthesia induced by the intravenous injections of pentobarbital and chloralose-urethan invariably stopped this activity throughout the preparation. The distribution of this time-dependent activity and the nature of the effect of the anesthetics suggests that this phenomenon is due to local pacemaker activity of groups of unitary smooth muscle cells.
Hemodynamic response to volume depletion in acutely uremic dogs
Authors: Daugirdas J. T. , Ing T. S. , Chen W. T. , Vestal R. E. , Izzo J. L. , Hano J. E. , Norusis M. J.
Published: December 2017

Hemodynamic response to volume depletion by isolated ultrafiltration was compared in uremic (U) and nonuremic (N) conscious dogs. Fluid was removed at a constant rate until mean arterial pressure (MAP) decreased to less than 80 mmHg. Initial MAP was higher in the uremic dogs [132 +/- 8.6 (SD) mmHg] than in nonuremic controls (106 +/- 12, P less than 0.001). Initial cardiac index [U 4.97 +/- 0.831 X min-1 X m-2, N 4.44 +/- 0.62] and total peripheral vascular resistance index [(TPRI) U 2,160 +/- 353 dyn X s X cm-5 X m-2, N 1,976 +/- 420] were slightly, but not significantly, higher in uremic animals. Initial central venous pressure, wedge pressure, and plasma norepinephrine level were greater in the uremic dogs. At the end point of volume depletion, both uremic and nonuremic animals had achieved similar levels of TPRI, despite greatly attenuated or absent increases in plasma renin activity in the uremic group. At end point, blood volumes and plasma norepinephrine levels were comparable. The increase in pulse rate was higher in the uremic animals (59 +/- 37 pulses/min) compared with controls (25 +/- 52, P less than 0.05). In an additional group of uremic dogs, cardiovascular responses to hemorrhage and isolated ultrafiltration were compared and found to be similar, after allowance for blood viscosity changes had been made. The data suggest that in acutely uremic conscious dogs, despite reduced renin-angiotensin responses, hemodynamic adaptation to rapid volume depletion is not impaired.
Adenosine as putative regulator of hepatic arterial flow (the buffer response)
Authors: Lautt W. W. , Legare D. J. , d'Almeida M. S.
Published: December 2017

In anesthetized cats, reduction of portal flow by occlusion of the superior mesenteric artery results in rapid increase in hepatic arterial (HA) flow that compensates for (buffers) 25.5 +/- 2.7% of the decreased portal flow. The hypothesis tested is that adenosine concentration produced near the HA resistance vessels is regulated by washout into portal vessels in intimate contact with the HA. Reduced portal flow leads to accumulation of adenosine and HA dilation. Several criteria for this hypothesis are met. First, adenosine is a potent dilator of the HA. Second, portal blood has access to HA resistance vessels as shown by a marked dilator effect of adenosine infused into the portal vein; it is therefore possible for adenosine produced locally to diffuse into portal blood. Third, dipyridamole potentiated the dilator response to adenosine as well as potentiating the buffer response from a 23% compensation for reduced portal flow to 34%. Fourth, 1-methyl-3-isobutylxanthine (MIX) antagonized exogenous adenosine and reduced the buffer response from 19% down to 5%. These data strongly support the hypothesis that the hepatic arterial buffer response is mediated by local concentrations of adenosine that are controlled by the rate of washout into portal blood.
Nonuniformity of inner and outer systolic wall thickening in conscious dogs
Authors: Gallagher K. P. , Osakada G. , Matsuzaki M. , Miller M. , Kemper W. S. , Ross J.
Published: December 2017

Transmural differences in systolic wall thickening were analyzed in 13 conscious dogs by implanting sonomicrometers to continuously measure total wall thickness (WT) and outer WT approximately half the distance through the myocardium at a closely adjacent location. Inner WT was derived by subtraction of outer WT from total WT. Outer wall measurements spanned, on average, the outer 44 +/- 10% (+/- SD) of the wall; derived inner wall measurements spanned the remaining 56 +/- 10%. At rest the fractional contribution (FC) of the outer wall to total systolic wall thickening was 29 +/- 9%, which was significantly less than the FC of the inner wall, 71 +/- 9%. These data are in good agreement with simplified modeling of a cross section of the left ventricle as two concentric rings that predicts that the FC of inner and outer halves of the wall should be approximately 67 and 33%, respectively. During treadmill exercise, the extent of both inner and outer thickening increased significantly (30 and 29%, respectively) but the relative FC of the inner and outer wall remained the same. The data indicate that systolic wall thickening is nonuniform and that this nonuniformity remains constant during the increased inotropic and chronotropic stimulation associated with exercise.
Transmural distribution of intramyocardial pressure measured by micropipette technique
Authors: Heineman F. W. , Grayson J.
Published: December 2017

A technique is presented for measuring intramyocardial pressure (IMP) in beating hearts using the servo-nulling pressure transducer equipped with polyethylene micropipettes (ID less than 12 micron). The static and dynamic response characteristics of the system were tested in a pressurized, saline-filled container as well as in a pressurized, hollow, gelatin cylinder. The system was then used to measure IMP in vivo in the hearts of 12 dogs during stable cardiac performance and with aortic constriction. In vitro response characteristics were found to be satisfactory for accurate reproduction of cardiovascular waveforms. Peak systolic IMP was not found to exceed the simultaneously recorded left intraventricular pressure (LVP). Furthermore, the slope of the regression line relating the IMP to LVP during systole is linearly related (slope 0.98) to the depth of the micropipette tip in the ventricular wall, as normalized to total wall thickness. Diastolic IMP ranged between 1 +/- 1 (minimum during the cardiac cycle) and 4 +/- 2 mmHg (end diastolic) at associated LVP of 2 +/- 2 and 5 +/- 2 mmHg (mean +/- SD), respectively.
Peak isovolumic pressure-volume relation of puppy left ventricle
Authors: Suga H. , Yamada O. , Goto Y. , Igarashi Y.
Published: December 2017

We studied peak isovolumic pressure-volume (PV) relation of the left ventricle in 3-mo-old mongrel puppies. A puppy heart was excised and cross circulated with an adult dog. Left ventricular pressure and volume were measured with a water-filled balloon. Peak isovolumic PV curve in control contractile state was convex upward, reaching a maximum pressure of 130 mmHg. Epinephrine (0.6 microgram/min intracoronary) shifted the curve leftward and up to a maximum pressure of 160 mmHg. Propranolol (0.8 mg intracoronary) shifted it rightward and down to a maximum pressure of 110 mmHg. These PV curves were reasonably fitted by an asymptotic equation: P = A (1 - exp[-B (V - Vd)]), where V was normalized volume for 100 g left ventricle and Vd (6 ml/100 g) was V at which peak pressure was zero. A and B are regression coefficients. A was 149, 169, and 120 mmHg, and B was 0.16, 0.19, and 0.06 ml, respectively, in control, enhanced, and depressed contractile states. These changes in A and B were statistically significant. We conclude that the puppy left ventricular peak isovolumic PV curve is convex upward and shifts sensitively with inotropic changes.
Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle
Authors: Rubanyi G. M. , Vanhoutte P. M.
Published: December 2017

Experiments were designed to determine the role of oxygen-derived free radicals in modulating contractions of vascular smooth muscle and endothelium-mediated relaxations to acetylcholine. The effects of generating or scavenging these radicals were studied in rings of canine coronary arteries suspended for isometric tension recording. Xanthine oxidase plus xanthine caused relaxations, which were greater in rings with endothelium than in rings without endothelium; the relaxations were not affected by superoxide dismutase or mannitol, but could be prevented by catalase. Xanthine oxidase plus xanthine depressed endothelium-mediated relaxations to acetylcholine; this effect was prevented by superoxide dismutase, but was not affected by catalase or mannitol. Exogenous hydrogen peroxide induced catalase-sensitive relaxations, which were depressed by the removal of the endothelium. Superoxide dismutase evoked catalase-sensitive relaxations only in rings with endothelium. Endothelium-mediated relaxations to acetylcholine were slightly depressed by superoxide dismutase or catalase alone; the combination of the two enzymes or mannitol caused a major shift to the right of the concentration-response curve to acetylcholine. In rings without endothelium, relaxations caused by sodium nitroprusside were not affected by the scavengers (alone or in combination) but were augmented by xanthine oxidase plus xanthine. These data suggest that the endothelium-derived relaxing factor released by acetylcholine is not likely to be an oxygen-derived free radical; hydrogen peroxide has a direct inhibitory action on coronary arterial smooth muscle and triggers endothelium-dependent relaxations; and superoxide anions depress and hydroxyl radicals facilitate endothelium-dependent relaxations caused by activation of muscarinic receptors.
Flow-induced release of endothelium-derived relaxing factor
Authors: Rubanyi G. M. , Romero J. C. , Vanhoutte P. M.
Published: December 2017

To analyze the potential mediator(s) involved in flow-induced endothelium-dependent vasodilation, we measured the wall tension of intraluminally perfused canine femoral artery segments and compared the content of 6-ketoprostaglandin F1 alpha (determined by radioimmunoassay) and the relaxing activity of the effluent (determined by bioassay on canine coronary artery rings). During perfusion at a steady flow of 2 ml/min the effluent contained 6-keto-prostaglandin F1 alpha and relaxed the bioassay rings. Sudden increase in steady flow rate to 4 ml/min, or the introduction of pulsatile flow, increased the release of 6-keto-prostaglandin F1 alpha and induced further relaxations of the bioassay ring. No relaxations were observed with the effluent passing through a femoral artery segment without endothelium. Indomethacin significantly depressed the release of 6-keto-prostaglandin F1 alpha during increases in flow but had no significant effect on the relaxing activity of the effluent. In the presence of indomethacin, increases in flow produced significant relaxation in the perfused femoral artery segments with endothelium. Superoxide dismutase restored the relaxing activity of the effluent during increases in flow at a transit time of 30 seconds. These data demonstrate that in addition to prostacyclin, flow triggers the release of another relaxing substance (or substances) from vascular endothelial cells that has characteristics similar to the endothelium-derived relaxing factor released by acetylcholine.
Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats
Authors: Itaya Y. , Suzuki H. , Matsukawa S. , Kondo K. , Saruta T.
Published: December 2017

The antihypertensive effect of blockade of the brain renin-angiotensin system (brain RAS) was investigated in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Continuous intracerebroventricular (ICV) administration of SQ14225 (SQ; 1.25 micrograms X 0.5 microliter-1 X h-1) for 7 days attenuated the increase in blood pressure (99 +/- 5 vs. 116 +/- 4 mmHg on the 7th day) and also reduced the elevation of blood pressure (157 +/- 7 vs. 138 +/- 6 mmHg) in these hypertensive rats. Attenuation of increasing blood pressure in the developing phase following ICV SQ treatment was accompanied by decrease of fluid intake and prevention of elevation of the plasma vasopressin. In the established phase, in addition to reduction of the plasma vasopressin and decrease of fluid intake, restoration of the impaired baroreceptor reflexes was brought about by ICV SQ treatment. These results indicate that the brain RAS strongly influences the regulation of blood pressure in DOCA-salt hypertensive rats and that its mechanism of action is closely related to changes in sodium excretion, vasopressin, and the baroreceptor reflexes.
Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation
Authors: Burke T. M. , Wolin M. S.
Published: December 2017

Hydrogen peroxide produces concentration-dependent relaxation of precontracted isolated bovine intrapulmonary arterial rings by a mechanism which is independent of the endothelium or prostaglandin mediators. Relaxant responses to hydrogen peroxide concentrations of up to 100 microM were markedly attenuated by the inhibitor of soluble guanylate cyclase activation, methylene blue (10 microM). Micromolar concentrations of hydrogen peroxide elicit time- and concentration-dependent increase in arterial levels of guanosine 3',5'-cyclic monophosphate that are associated with decreases in force. Soluble guanylate cyclase activity is markedly activated by enzymatically generated hydrogen peroxide in a manner that is most closely associated with the concentration of catalase present in the assay, by a mechanism that is inhibited by superoxide anion and the inactivation of catalase. Our data are most consistent with the involvement of compound I, a species of catalase formed during the metabolism of peroxide, in the mechanism of guanylate cyclase activation. The nature of this mechanism of arterial relaxation suggests that it could contribute to the regulation of pulmonary vascular tone by oxygen tension.
Hemodynamic regulation in SHR: investigation by spectral analysis
Authors: Akselrod S. , Eliash S. , Oz O. , Cohen S.
Published: December 2017

This work is based on the premise that hypertension in the spontaneously hypertensive rat (SHR) is a consequence of an imbalance in autonomic cardiovascular control. Spontaneous, instantaneous fluctuations in heart rate (HR) and arterial blood pressure (ABP) were studied by spectral analysis in age-matched groups of SHR and normotensive Wistar-Kyoto (WKY) rats. Continuous recordings of ABP and HR made in conscious, unrestrained, young 1-, 2-, 3-, and 6-mo-old rats show that power spectra of HR fluctuations were similar in both strains, whereas ABP fluctuations were significantly different in the low, presumably vasomotor frequency range being reduced in SHR as compared with age-matched WKY rats. In 1-mo-old rats, the difference between strains became smaller with urethan anesthesia and disappeared with spinalization, suggesting that it might have originated in some disparity between the strains at the level of the central nervous system. Low doses of phentolamine elicited a fall in low-frequency ABP fluctuations of WKY but a rise in SHR, whereas larger doses produced a fall in the power of both. In SHR, reduction in the power spectrum of ABP fluctuations in the presence of unaltered HR fluctuations may indicate an impaired control of sympathetic drive to resistance vessels compared with WKY. Note that in young SHR, hypertension also cannot be detected by conventional measurement. Fluctuations in ABP in WKY may reflect an optimal level of sympathetic activity; reduction in fluctuations may be associated with an increase or decrease in sympathetic activity at the vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Transmural anoxic wave front and regional dysfunction during early ischemia
Authors: Kanaide H. , Taira Y. , Nakamura M.
Published: December 2017

The relative time courses of early changes in myocardial metabolism and function during anoxia, global ischemia, and regional ischemia were compared in isolated rat hearts. Transmural anoxic wave front was determined with NADH fluorescence photography, and oxygen saturation of myoglobin and dynamic systolic wall thickening were measured with spectrophotometry of light transmitted through the left ventricular free wall. In all three treatments, anoxic wave front first appeared in the subendocardium and reached the epicardial half of the myocardium in 10 s, when oxygen saturation of myoglobin decreased by 50% and tissue ATP and creatine phosphate remained at aerobic levels. During this period, systolic wall thickening decreased gradually in anoxia and global ischemia, whereas a marked decrease in systolic wall thickening and appearance of dyskinesia (wall thinning) occurred in regional ischemia. Thus the early extension of anoxic wave front and metabolic changes are similar with all three treatments, and dyskinesia, observed only in case of regional ischemia, occurs when the inner half is ischemic or anoxic.
alpha-ANP alters reflex control of lumbar and renal sympathetic nerve activity and heart rate
Authors: Imaizumi T. , Takeshita A. , Higashi H. , Nakamura M.
Published: December 2017

This study examined the effects of synthetic alpha-rat atrial natriuretic peptide (alpha-rANP) on arterial pressure (AP), heart rate (HR), and renal and lumbar sympathetic nerve activity (SNA) in rats with intact arterial baroreceptors before and after bilateral vagotomy and in those with sinoaortic denervation before and after vagotomy. In intact rats, alpha-rANP decreased AP, which was accompanied by the decrease in renal SNA ad HR and no change in lumbar SNA. In contrast, the increase in lumbar SNA and HR occurred during hypotension caused by nitroglycerin. In rats with intact arterial baroreceptors and vagi sectioned, renal and lumbar SNA and HR did not change during hypotension with alpha-rANP. In addition, alpha-rANP did not alter the gain of arterial baroreflex control of lumbar SNA in these rats. In rats with sinoaortic denervation, alpha-rANP decreased HR and renal and lumbar SNA before vagotomy but did not change them after vagotomy. These results suggest, first, that alpha-rANP activates vagal afferents and thereby inhibits renal and lumbar SNA and HR and, second, that alpha-rANP may reset arterial baroreflex control of SNA and HR to a lower pressure range.
Effects of thyroid state on venous compliance and left ventricular performance in rats
Authors: Gay R. G. , Raya T. E. , Lancaster L. D. , Lee R. W. , Morkin E. , Goldman S.
Published: December 2017

The cardiovascular system of hypothyroid, normal, and hyperthyroid rats was studied by evaluation of the peripheral venous circulation and left ventricular (LV) systolic and diastolic performance in rats. Cardiac index (CI) and CI during a volume load were measured in open-chest rats. When compared with control, hypothyroid rats showed a decrease in heart rate, aortic pressure, LV systolic pressure, first derivative for LV pressure (LV dP/dt), CI, and CI during a volume load. LV pressure-volume relation was shifted to the right, muscle stiffness was unchanged, and LV relaxation was prolonged. There was a decrease in mean circulatory filling pressure (MCFP) to 6.3 +/- 0.2 from 7.6 +/- 0.2 mmHg in control rats. This was associated with an 11% decrease in unstressed vascular volume and 12% decrease in total blood volume but no change in venous compliance. In hyperthyroid rats there was an increase in heart rate, LV systolic pressure, LV dP/dt, CI, and CI during a volume load. LV chamber stiffness was increased, but muscle stiffness and LV relaxation were unchanged. There was an increase in MCFP to 9.5 +/- 0.3 mmHg and a decrease in venous compliance to 2.65 +/- 0.12 compared with 3.20 +/- 0.09 ml.mmHg-1.kg-1 in control rats. Unstressed vascular volume and total blood volume were unchanged. In conclusion, hyperthyroid rats have augmented LV systolic function and altered diastolic function which, combined with changes in the venous circulation, result in increased venous return and thus cardiac output. In hypothyroid rats both LV systolic and diastolic function are altered. When combined with changes of the venous circulation the changes result in a decrease in cardiac output.
Volume overload hypertrophy in a closed-chest model of mitral regurgitation
Authors: Kleaveland J. P. , Kussmaul W. G. , Vinciguerra T. , Diters R. , Carabello B. A.
Published: December 2017

Chronic volume overload hypertrophy as seen in mitral regurgitation in humans eventually may cause left ventricular dysfunction. Longitudinal study of the mechanisms leading to such dysfunction is difficult in humans and more easily performed in an animal model. In this study, we describe a canine model of volume overload hypertrophy produced by mitral regurgitation. An arterially placed grasping forceps was used to disrupt mitral chordae or leaflets; thus mitral regurgitation was produced without the need for thoracotomy. Eleven of 22 dogs had severe mitral regurgitation (regurgitant fraction greater than 0.50) and survived for greater than or equal to 3 mo (average 9.2 +/- 6 mo) after the production of mitral regurgitation. At 3 mo, end-diastolic volume increased from 48 +/- 9 to 85 +/- 19 ml, P less than 0.01. Left ventricular mass increased from 71 +/- 13 to 90 +/- 10 g, P less than 0.01. Left ventricular end-diastolic pressure increased from 9 +/- 3 to 19 +/- 6 mmHg, P less than 0.01. Cardiac output decreased from 2.3 +/- 0.61 to 1.80 +/- 0.64 l/min, P less than 0.05. The mass-to-volume ratio decreased from 1.44 +/- 0.17 to 1.09 +/- 0.13, P less than 0.01. We conclude that this closed-chest model of chronic mitral regurgitation produces significant eccentric cardiac hypertrophy. Despite a doubling of end-diastolic volume, there was a fall in cardiac output and a rise in left ventricular end-diastolic pressure, suggesting cardiac decompensation.
Conservation of photoperiod-responsive mechanisms in humans
Authors: Wehr T. A. , Moul D. E. , Barbato G. , Giesen H. A. , Seidel J. A. , Barker C. , Bender C.
Published: December 2017

In animals, circadian pacemakers respond to seasonal changes in day length by making corresponding adjustments in the durations of diurnal and nocturnal periods of circadian rhythms; these adjustments mediate effects of photoperiod on breeding and other seasonally recurring phenomena. Little is known about photoperiod responses of human circadian pacemakers. To investigate this question, we recorded and compared circadian rhythm profiles of 15 individuals after chronic exposures to short (8 h) and long (14 h) nights. As occurs in animals, durations of nocturnal periods of active melatonin secretion (11.9 +/- 1.6 vs. 10.3 +/- 1.3 h, df = 14, t = 4.583, P < 0.0005, paired t test), high prolactin secretion (12.9 +/- 2.1 vs. 9.9 +/- 2.2 h, df = 11, t = 2.917, P < 0.01), and sleep (10.6 +/- 0.8 vs. 7.6 +/- 0.4 h, df = 14, t = 17.122, P < 0.0005) were longer after exposure to long nights than after short ones. Durations of nocturnal periods of low rectal temperature (11.6 +/- 2.3 vs. 9.5 +/- 1.6 h, df = 12, t = 3.912, P < 0.001) and rising cortisol secretion (10.8 +/- 1.6 vs. 9.3 +/- 1.9 h, df = 14, t = 3.130, P < 0.005) were also longer. Some of these differences persisted during 24-h periods of enforced wakefulness in constant dim light, indicating that prior exposure to the two regimes induced abiding changes in the timing of internal processes, such as circadian pacemaker oscillations, that control the durations of nocturnal and diurnal periods of the rhythms.
Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade-induced hypertension
Authors: Qiu C. , Engels K. , Baylis C.
Published: December 2017

Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1-adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1-adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO-blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1-adrenoceptor and AT1 stimulation.
Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the rat
Authors: Szmydynger-Chodobska J. , Chodobski A. , Johanson C. E.
Published: December 2017

Postnatal developmental changes in blood flow to choroid plexuses of the lateral (LVCP) and fourth (4VCP) ventricles and cerebral cortex were studied in pentobarbital-anesthetized rats at 2, 3, 5, and 7-8 wk. Blood flow was measured by indicator fractionation with N-isopropyl-p-[125I]iodoamphetamine as the marker. Blood flow to the LVCP and 4VCP was 2.5 +/- 0.1 and 2.7 +/- 0.1 ml.g-1.min-1, respectively, and did not change between the 2nd and 3rd wk. However, it increased by 34% between the 3rd and 5th wk. From the age of 5 wk on, 4VCP was characterized by higher blood flow rates than LVCP. Cerebral cortical blood flow gradually increased between the 2nd and 5th wk. There was no difference in cortical blood flow between 5-wk-old and adult animals. The changes in choroidal blood flow likely represent a continuing adjustment of the choroidal vascular system to steadily increasing secretory capabilities of the maturing choroidal epithelium.
Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries
Authors: Michel J. B. , Heudes D. , Michel O. , Poitevin P. , Philippe M. , Scalbert E. , Corman B. , Levy B. I.
Published: December 2017

The consequences of hypertension and aging on cardiovascular structure and function are reputed to be similar, suggesting that blood pressure plays a role in the aging process. However, the exact relationship between aging, blood pressure, and the arterial structure-function relationship has not been demonstrated. To test the effects of aging, renin-angiotensin system, and pressure on the arterial wall, 20 normotensive male WAG/Rij rats were killed at 6, 12, 24, and 30 mo of age and compared with similar groups treated with an angiotensin (ANG)-converting enzyme inhibitor (ACEI), perindopril. Arterial function was determined by a systemic hemodynamic study and by in situ measurement of carotid compliance. Arterial wall structure was determined by histomorphometric and biochemical methods. Aging did not significantly modify blood pressure, but ACE inhibition decreased blood pressure significantly from 6 to 30 mo. Plasma renin activity decreased with age and increased with ACEI. Plasma atrial natriuretic factor increased with age and was significantly decreased with ACEI. Absolute and relative left ventricular weight increased with age, and ACEI delayed these increases. Arterial wall stiffness increased with age, as shown by a significant decrease in systemic and local arterial compliance and by an increase in aortic characteristic impedance. The increase in carotid wall compliance after poisoning of smooth muscle contractile function (KCN) was greater in young (6- and 12-mo old) than in old (24- and 30-mo old) rats. Chronic ACEI treatment increased basal carotid compliance values slightly and did not change KCN carotid compliance. The aortic and carotid luminal size increased regularly with age. Aging was associated without any change in absolute elastin content. In contrast, collagen content increased with aging. Aging was also associated with an increase in medial thickness. Medial thickening was mainly due to smooth muscle hypertrophy. Aging was associated with intimal proliferation, which became progressively thicker and collagen rich. ACEI treatment did not prevent aortic lumen enlargement but significantly postponed the increase in medial and intimal thickening. Biochemical determinations of the aortic wall components confirmed the morphometric data. In conclusion, the age-dependent large artery enlargement and stiffening were observed both in normotensive rats and in those rats whose blood pressure was lowered by ACEI. This suggests that aging and blood pressure affect arterial wall structure and function by different mechanisms.
N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs
Authors: Ruiz F. J. , Salom M. G. , Ingles A. C. , Quesada T. , Vicente E. , Carbonell L. F.
Published: December 2017

Recently, in vivo and in vitro studies have implicated nitric oxide as a mediator of the vascular effects of angiotensin-converting enzyme inhibitors (ACEIs). In the present study we hypothesized that N-acetyl-L-cysteine (NAC), by increasing the availability of reduced sulfhydryl groups, would enhance the antihypertensive response to the ACEIs captopril and enalaprilat by a mechanism dependent on nitric oxide. The experiments were performed on instrumented, indomethacin-pretreated, awake spontaneously hypertensive rats (SHRs). Thirty minutes after a bolus of captopril (10 mg/kg iv) was administered, blood pressure decreased from 167 +/- 5 to 147 +/- 6 mmHg (n = 8). The pretreatment with the donor of thiol groups NAC (300 mg/kg iv) potentiated the depressor response to captopril because blood pressure decreased from 172 +/- 3 to 139 +/- 4 mmHg (n = 6). At the dose of 60 micrograms/kg iv, the ACEI enalaprilat did not acutely modify the blood pressure of SHRs (from 172 +/- 5 to 167 +/- 4 mmHg; n = 6). However, when the SHRs were pretreated with NAC, the same dose of enalaprilat significantly reduced blood pressure from 176 +/- 5 to 151 +/- 5 mmHg (n = 6). This potentiation of the depressor response to ACEIs, due to NAC, was not observed when SHRs were pretreated with the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 50 micrograms.kg-1.min-1 iv). The results of this study suggest that NAC, a donor of sulfhydryl groups, potentiates the antihypertensive response to captopril and enalaprilat in SHR by a nitric oxide-dependent mechanism.
CCK/gastrin-like immunoreactivity in brain and gut, and CCK suppression of feeding in goldfish
Authors: Himick B. A. , Peter R. E.
Published: December 2017

The presence and distribution of cholecystokinin (CCK)/gastrin-like immunoreactive (IR) material were examined in the goldfish brain and gut. In the forebrain, CCK/gastrin-like IR fibers and perikarya were localized to nuclei of predominantly the ventral telencephalon and diencephalon; more dorsal forebrain regions contained only few, thin-beaded, sparsely distributed IR fibers. CCK/gastrin-like IR was specifically detected in the preoptic hypothalamus, including the nucleus entopeduncularis, nucleus preopticus periventricularis, and nucleus preopticus. Of all brain regions examined, the highest concentration of CCK/gastrin-like IR staining was consistently observed in nuclei of the ventroposterior and inferior lobes of the hypothalamus. Within the gut, both nerve fibers and endocrine cells contained CCK/gastrin-like IR. The abundance of CCK/gastrin-like IR material within brain areas known to represent the feeding center of fish, as well as the presence of IR material within the gut, suggests that CCK may influence feeding behavior in fish. When injected either intraperitoneally or into the third brain ventricle into goldfish, sulfated CCK-8 (CCK-8s) suppressed food intake. The nonsulfated form of CCK-8 was not as effective as CCK-8s in suppressing feeding after intraperitoneal injection. No consistent changes were observed in circulating serum growth hormone or gonadotropin levels after either intraperitoneal or intracerebroventricular injection of CCK-8s. These studies demonstrate for the first time that CCK-8s is effective in acutely suppressing feeding behavior in fish when administered either peripherally or centrally into the third brain ventricle.
Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture
Authors: Lu M. , Wagner G. F. , Renfro J. L.
Published: December 2017

The effects of several hormones on transepithelial Pi transport were determined in primary monolayer cultures of winter flounder proximal tubule epithelium in Ussing chambers. Salmon stanniocalcin (STC) had a dose-dependent stimulatory effect on net Pi reabsorption within the normal plasma hormone concentration range, 12.5-50 ng/ml (0.25-1.0 nM). Net Pi transport was significantly altered by STC (200 ng/ml) within 30 min and progressively increased from slight net secretion (0.26 +/- 0.744 nmol.cm-2.h-1) in untreated controls to net reabsorption (1.96 +/- 0.729 nmol.cm-2.h-1) after 3 h. The STC effect was mimicked by 10 microM forskolin, whereas 10 microM H-89, a highly specific protein kinase A inhibitor, significantly decreased both STC- and forskolin-induced Pi reabsorption. The release of adenosine 3',5'-cyclic monophosphate (cAMP) was increased more than twofold after a 1-h exposure to STC. This hormone had no effect on transepithelial Ca2+ transport. The results indicate that STC directly stimulates net renal Pi reabsorption by a cAMP-dependent pathway. In addition to STC, bovine parathyroid hormone (100 nM) and ovine prolactin (100 nM) significantly increased net Pi reabsorptive flux.
Circadian and ultradian rhythms of peripheral prolactin concentrations in lactating dairy cows
Authors: Lefcourt A. M. , Akers R. M. , Wood D. L. , Bitman J.
Published: December 2017

To investigate possible circadian and ultradian periodicities for peripheral prolactin in lactating dairy cows, integrated 15-min blood samples taken sequentially over 48 h from six cows were analyzed by radioimmunoassay. Cows were housed in an environmental chamber at 19 degrees C with lights on 0700 to 2300, fed daily at 0900, and milked at 0800 and 2000. Peripheral concentrations exhibited sinusoidal circadian rhythms. For two cows, a nadir of 15 ng/ml occurred around 1900 and a zenith of 29 ng/ml around 0730. For four cows, circadian rhythms were 180 degrees out of phase, with a nadir of 28 ng/ml around 0840 and a zenith of 40 mg/ml around 1920. Ultradian peaks, which varied in amplitude within and among animals, showed no consistent relationship with either milking or feeding. Spectral analyses indicated rhythms around 100 min for the first two animals and 150 min for the four animals. In conclusion, there were no simple relations between prolactin rhythms and lights on or lights off. Further, results suggest that changes in the phase of circadian rhythms may be associated with changes in the periods of ultradian rhythms.
Glucocorticoids and insulin: reciprocal signals for energy balance
Authors: Strack A. M. , Sebastian R. J. , Schwartz M. W. , Dallman M. F.
Published: December 2017

Signals that regulate long-term energy balance have been difficult to identify. Increasingly strong evidence indicates that insulin, acting on the central nervous system in part through its effect on neuropeptide Y (NPY), inhibits food intake. We hypothesized that corticosteroids and insulin might serve as interacting, reciprocal signals for energy balance, acting on energy acquisition, in part through their effects on hypothalamic NPY, as well as on energy stores. Because glucocorticoids also stimulate insulin secretion, their role is normally obscured. Glucocorticoids and insulin were clamped in adrenalectomized rats with steroid replacement and streptozotocin-induced diabetes. Glucocorticoids stimulated and insulin inhibited NPY mRNA and food intake. Glucocorticoids inhibited and insulin increased energy gain as determined by the change in body weight. When adrenalectomized diabetic rats were treated, corticosterone stimulated and insulin inhibited food intake, and, respectively, inhibited and increased overall energy gain. More than 50% of the variance was explained by regression analysis of the two hormones on food intake and body weight. Thus glucocorticoids and insulin are major, antagonistic, long-term regulators of energy balance. The effects of corticosterone and insulin on food intake may be mediated, in part, through regulation of hypothalamic NPY synthesis and secretion.
Sex differences in blood flow distribution of normothermic and heat-stressed rabbits
Authors: Lublin A. , Wolfenson D. , Berman A.
Published: December 2017

Sex differences in blood flow (BF) distribution of male and female mature laboratory rabbits were determined in normothermic and heat-stressed states. Animals were anesthetized with alpha-chloralose, and BF distribution was determined by radioactive microspheres in the thermoneutral state and then again during hyperthermia after 2 h of heat exposure. Cardiac output did not change in either sex during heat stress. BF to the toe and ear skin and to nasal turbinates was lower in females than in males, whereas that to the diaphragm, sternum, intercostal muscles, spleen, and skeletal muscles was higher in females. A thermal state-by-sex interaction was detected in several organs, indicating that during heat stress in males, BF is significantly higher than in the controls, whereas in females a decline, no change, or only a slight increase was recorded. Males did not exhibit any decrease in inner organ BF during heat stress, whereas females did. Results show sex differences in BF distributions under normothermia and hyperthermia, suggesting that males and females differ in their BF regulation in both peripheral organs, which are active in heat dissipation, and inner body organs.
Metabolic adaptations for desert survival in the Bedouin goat
Authors: Choshniak I. , Ben-Kohav N. , Taylor C. R. , Robertshaw D. , Barnes R. J. , Dobson A. , Belkin V. , Shkolnik A.
Published: December 2017

Energy conservation is a key adaptation for desert survival in the Bedouin goat. When food is scarce, metabolism is reduced and body weight can be maintained indefinitely on less than one-half of normal intake. We hypothesized that metabolism would be turned down during both rest and exercise, but it was not. It was low when animals rested and returned to normal during exercise. We expected catecholamines and thyroid hormones would modulate metabolism, but they did not. The reduction in metabolism preceded any change in thyroid hormone concentrations, and infusions of epinephrine did not restore reduced metabolism to normal levels. Finally, we expected the gut would be the major organ system involved in the metabolic reduction because less food is eaten, processed, and absorbed. Contrary to our expectations, we found that muscle is the primary organ system responsible for the reduction. It appears that the adaptations of the Bedouin goat for surviving on limited food supplies involve different organ systems and different modulators to reduce metabolism from those known for other mammals.
Changes in eating behavior and thermogenic activity following inhibition of nitric oxide formation
Authors: De Luca B. , Monda M. , Sullo A.
Published: December 2017

The effects of the inhibition of nitric oxide (NO) production on eating behavior and thermogenesis were evaluated in the present experiments. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO production, was injected intraperitoneally or intracerebroventricularly, and food intake, oxygen consumption rate, and interscapular brown adipose tissue (BAT) temperature were evaluated in conscious rats. The firing rate of sympathetic nerves innervating interscapular BAT was recorded in urethan-anesthetized animals. L-NAME, intraperitoneally injected, decreased food intake, oxygen consumption, temperature, and firing rate of sympathetic nerves innervating interscapular BAT. Intracerebroventricular injection of L-NAME decreased food intake and enhanced oxygen consumption, temperature, and firing rate of sympathetic nerves innervating BAT. The latter changes were similar to those found after lateral hypothalamic lesions. The opposite changes in oxygen consumption, temperature, and sympathetic activity of BAT that followed L-NAME injection through the two different routes were probably due to different effects of the molecule on sympathetic output. Impaired brain production of NO, which followed intracerebroventricular L-NAME, directly increased sympathetic activity, whereas the same activity that followed intraperitoneal L-NAME was depressed by increased blood pressure, which was elicited by the impaired peripheral production of NO.
Salt discriminability is related to number of regenerated taste buds after chorda tympani nerve section in rats
Authors: St John S. J. , Markison S. , Spector A. C.
Published: December 2017

Transection of the chorda tympani nerve (CTX) impairs taste-guided discrimination of NaCl from KCl in rats. We wanted to determine whether this discrimination recovers after chorda tympani regeneration. Experiment 1 showed that few taste buds regenerated 14 days after CTX, whereas substantial regeneration occurred 42 days after surgery. Experiment 2 demonstrated that rats trained before CTX could clearly discriminate the two salts when tested starting 49 days after surgery, whereas rats tested starting 8 days after surgery were severely impaired in this task. Rats tested starting 28 days after CTX were unimpaired, moderately impaired, or severely impaired on the discrimination task. Overall, discrimination performance was significantly related to the number of regenerated taste buds. Unilaterally transected rats tested shortly after surgery were nearly as competent as controls. These results indicate that rats can recover the ability to discriminate NaCl from KCl after regeneration of anterior tongue taste buds.
Resistance exercise-induced fluid shifts: change in active muscle size and plasma volume
Authors: Ploutz-Snyder L. L. , Convertino V. A. , Dudley G. A.
Published: December 2017

The purpose of this study was to test the hypothesis that the reduction in plasma volume (PV) induced by resistance exercise reflects fluid loss to the extravascular space and subsequently selective increase in cross-sectional area (CSA) of active but not inactive skeletal muscle. We compared changes in active and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance imaging (MRI) was used to quantify muscle involvement in exercise and to determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add), hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was determined using exercise-induced contrast shift in spin-spin relaxation time (T2)-weighted MR images immediately postexercise. Alterations in muscle size were based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans blue dye were used to estimate changes in PV. Muscle CSA and PV data were obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A hierarchy of muscle involvement in exercise was found such that VS > Add > Ham > RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add muscle groups were increased 10 and 5%, respectively, immediately after exercise in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately following exercise. The absolute loss of PV was correlated (r2 = 0.75) with absolute increase in muscle CSA immediately postexercise, supporting the notion that increased muscle size after resistance exercise reflects primarily fluid movement from the vascular space into active but not inactive muscle.