摘要:

Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that l-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous l-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, for this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor synthesis. Accordingly, we designed a study to determine whether exogenous l-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acetylcholine (0.3–9.0 μg/kg/min) and nitroprusside (0.3–9.0 μg/kg/min) were studied before and during intravenous administration of l-arginine (10 mg/kg/min), d-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. l-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. l-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor d-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous l-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Conscious normotensive and two-kidney, one-clip Goldblatt hypertensive rabbits were studied to determine the sensitivity of the arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate. The relations of the mean arterial pressure-RSNA and mean arterial pressure-heart rate were examined over a wide range of blood pressures produced by infusions of phenylephrine and nitroglycerin. The maximum slope obtained by logistic function analysis was considered to represent the baroreflex sensitivity. In the early hypertensive group (n=8; mean arterial pressure±SEM, 88±2 mm Hg) on day 5 after renal clip application, the maximum slope of the mean arterial pressure-RSNA relation was - 11.3±1.2, which was significantly greater than that of the sham normotensive group (−6.9±0.3,p<0.05). The maximum slope (−4.3±0.2) of the mean arterial pressure-RSNA relation in the late hypertensive group (n=8; mean arterial pressure, 96±3 mm Hg) on day 21 after renal clipping was significantly smaller than that of another sham group (−7.2±0.2,p<0.05). In contrast to these changes in the baroreflex control of RSNA, the control of heart rate was attenuated according to the magnitude of mean arterial pressure. To elucidate the mechanisms underlying the potentiated baroreflex, the effects of endogenous neuropeptides were investigated. First, plasma concentrations of angiotensin II and arginine vasopressin that are known to affect the baroreflex were determined. Plasma concentrations of vasopressin (3.1±0.6 pg/ml) as well as of angiotensin II (34±7 pg/ml) were increased in the early hypertensive group, and the plasma vasopressin returned to a similar level to the sham group in the late hypertensive group (1.3±0.4 pg/ml). Second, to study endogenous effects of these neuropeptides on the baroreflex, the maximum slopes of the baroreflex curves during infusions of antagonists for the peptides were determined in the early hypertensive group. The maximum slope of mean arterial pressure-RSNA during intravertebral arterial [Sar1, Ala8]-angiotensin II (−16.4±1.5) was significantly greater (p<0.05), whereas the maximum slope during intravertebral arterial infusion of d(CH2)5Tyr(Me)arginine vasopressin (−4.7±0.5) was significantly smaller (p<0.05) than that during vehicle infusion (−11.3±1.2). These results suggest that the baroreflex control of RSNA was potentiated in the early phase of two-kidney, one-clip hypertension in conscious rabbits and that endogenous arginine vasopressin and angiotensin II, which counteract each other, were apparently involved in the potentiated baroreflex mechanism.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Our study was designed to determine the cardiac electrophysiological influence of vasoactive intestinal polypeptide (VIP) in conscious dogs. Dogs (n=8) were chronically instrumented with arterial and venous catheters, cervical vagal cooling coils, and right atrial and right ventricular bipolar epicardial pacing and recording electrodes. After autonomic blockade (10 mg/kg i.v. hexamethonium, 0.11 mg/kg i.v. atropine, and vagal cold blockade), VIP (50 and 100 pmol/kg/min i.v.) or isoproterenol (ISO) (250 and 500 pmol/kg/min i.v.) increased heart rate (maximum increases: VIP, 81.1±4.2 beats/min; ISO, 61.3±8.5 beats/min), decreased the atrial-ventricular interval (during constant atrial pacing) (VIP, −41.9±63 msec; ISO, −34.6±7.4 msec), shortened the atrial effective refractory period (VIP, −24.4±2.1 msec; ISO, −30.6±4.4 msec) and ventricular effective refractory period (VIP, −4.2±0.7 msec; ISO, −10.0±2.4 msec), and decreased mean arterial pressure (VIP, −51.9±4.0 mm Hg; ISO, −26.1±2.4 mm Hg). β-Adrenergic blockade with propranolol (1 mg/kg i.v.) eliminated the positive chronotropic and atrioventricular nodal dromotropic responses to bolus doses of ISO (30, 100, 300, and 1,000 pmol/kg i.v.) but did not affect the responses to VIP (10, 30, 100, and 300 pmol/kg i.v.). Comparable blood pressure decreases produced by sodium nitroprusside caused only minimal changes in heart rate, atrial-ventricular conduction times, and atrial and ventricular refractory periods. In three additional anesthetized dogs, after vagotomy and β-adrenergic blockade (1 mg/kg i.v. propranolol), VIP (100 pmol/kg/min i.v.) shortened the atrial-His interval but did not alter intra-atrial, intraventricular, or His-Purkinje conduction. Our findings combined with the demonstration by others of VIP-immunoreactive nerves innervating canine sinus nodal cells, atrioventricular nodal cells, and atrial and ventricular myocardial cells suggest that endogenous VIP may directly alter the electrical properties of the heart.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Several intracellular enzymes have been shown to have altered total activity or isoenzyme composition in cardiac hypertrophy. This study tests the hypothesis that the accumulation of the fetal-type (BB+MB) creatine kinase (CK) isoenzymes in hypertrophied adult myocardium is related to an increase in blood pressure. Consideration was made for the location, size, and hemodynamic load of the myocytes. By using the two-kidney, one-clip (2K1C) rat model of renal hypertension with and without hydralazine treatment, CK (total and isoenzyme), lactate dehydrogenase, and citrate synthase activities and myocyte size were measured. An increased heart weight/body weight ratio occurred in both untreated 2K1C rats (4.15±0.09) and hydralazine-treated 2K1C rats (4.12±0.13) as compared with control rats (3.25±0.10). Blood pressure was high only in untreated 2K1C rats (196±9 mm Hg), as compared with hydralazine-treated 2K1C rats (142±6 mm Hg) and control rats (135±3 mm Hg). Myocytes were isolated from five ventricular regions: left ventricular epicardial and endocardial free wall, left and right halves of the interventricular septum, and right ventricular free wall. Regional differences in normal and hypertrophied myocardium were demonstrated for morphological and biochemical parameters, with the greatest changes occurring in left ventricular endocardium. The shift in CK isoenzyme expression toward accumulating more BB+MB was greater in “hypertensive hypertrophy” (untreated 2K1C rats) than in “lnonhypertensive hypertrophy” (hydralazine-treated 2K1C rats). Calculations incorporating isolated myocyte volume showed that the cellular content of total CK remained the same during the hypertrophic process, accounting for a decrease in the tissue activity. Measurement of lactate dehydrogenase and citrate synthase activities suggests that hypertrophied myocardium has relatively higher glycolytic capacity and that this effect is exacerbated in the presence of high blood pressure. We conclude that increased blood pressure is more closely linked to the fetal CK isoenzyme shift than is hypertrophy alone.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Atrial natriuretic peptide is a potent dilator of aorta and renal and cerebral arteries and inhibits sympathetic tone in the heart in several mammalian species. We examined the possibility that a molecule related to porcine brain natriuretic peptide (pBNP), which acts at the same receptor sites as atrial natriuretic peptide, might provide an alternative source of natriuretic peptide to the cardiovascular system in the rat. An antiserum against pBNP demonstrated profuse immunoreactive innervation of the heart, cerebrovascular tree, and renal arteries. pBNP-like immunoreactive fibers ran in bundles along the surface of the heart, innervating the atria most heavily and penetrating the ventricular myocardium along the coronary arteries. There was greater density of innervation of the right side of the heart compared with the left, particularly in the ventricles, suggesting a parasympathetic origin. The entire cerebrovascular tree was innervated by immunoreactive pBNP fibers, with the densest concentration of immunoreactive fibers along the surface of the internal carotid, middle cerebral, posterior communicating, and anterior cerebral arteries. The proximal renal arteries were not innervated, but as they approached the kidney, they were invested by bundles of immunoreactive pBNP fibers. These axons followed the major branches of the renal artery into the kidney parenchyma, running along the surface of the arterioles up to their entrance into the renal glomeruli. No immunoreactive innervation of the aorta or proximal brachiocephalic, subclavian, or carotid arteries was seen. A substance related to pBNP may serve as a neuromodulator regulating cardiac output as well as blood flow in certain vascular beds.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study evaluated the effect of bilateral carotid chemodenervation on the cerebrovascular response to hypoxia in conscious rats. Cerebral blood flow was measured using 4-iodo[N-methyl-14C]antipyrine, and the total and perfused microvasculature was studied by injection of fluorescein isothiocyanate dextran and alkaline phosphatase staining. To maintain constant Pco2, hypoxia was achieved in chemoreceptor-intact rats by the use of 4% CO2-8% O2-88% N2and in chemodenervated rats by the administration of 8% O2-92% N2. Blood gas and hemodynamic parameters were similar in the two groups of rats. Chemodenervation had no significant effect on either resting blood flow or the perfused microvasculature during normoxia. A significant increase in cerebral blood flow (from 71±3 to 138±9 ml/min/100 g in control and from 91±5 to 127±7 ml/min/100 g in chemodenervated rats) and in the percent of cerebral arterioles and capillaries perfused occurred in both hypoxic control and chemodenervated rats. In chemoreceptor-intact rats, the greatest increase in blood flow and in perfused microvasculature occurred in caudal structures (medulla and pons) in comparison with rostral structures (cortex, thalamus, and hypothalamus). In chemodenervated rats, a similar increase in blood flow and perfused microvasculature occurred in all brain regions, with no regional differences. Thus, chemodenervation did not affect the overall cerebral blood flow or the microvascular response to hypoxia; however, rostral-to-caudal regional differences in the hypoxic response were lost after chemodenervation.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We determined the effects of mono-L-arginine-containing compounds on pial arterioles of anesthetized piglets. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. Diameter was determined during application of artificial cerebrospinal fluid containing no drugs and during application of 10−510−4, 10−3, and 10−2M l-arginine (ARG), l-arginine ethyl ester (AEE),Nα-benzoyl-L-arginine (NBA),Nα-benzoyl-L-arginine ester ethyl (BAEE), and l-citrulline (CIT). Initial diameters were 100-200 μm. All of these compounds dilated arterioles, but the threshold concentration needed to elicit dilation varied: 10−5M for NBA (n=5), 10−3M for AEE (n=9) and BAEE (n=6), and 10−2M for ARG (n=6) and CIT (n=4). Maximal responses were 15±8% for CIT, 17±4% for ARG, 19±8% for BAEE, 28±5% for NBA, and 27±6% for AEE. Indomethacin pretreatment (5 mg/kg i.v.) did not change arteriolar responses to AEE, NBA, and BAEE. However, coadministration of methylene blue (0.5±10−4M or 0.5±10−3M) abolished dilation to 10−3M AEE or BAEE and attenuated dilation to 10−5M NBA. In addition, coadministration of hemoglobin (0.4±10−4M) abolished dilation to AEE, BAEE, or NBA. Last, intravenous (5 mg/kg) and coadministration (10−3M) ofNG-methyl-L-arginine blocked dilation to NBA or AEE. We conclude that mono-L-arginine-containing compounds produce pial arteriolar dilation in piglets, possibly involving an endothelium-derived relaxing factor.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The purpose of this study was to test the hypothesis that prostaglandins released from vascular endothelial cells contribute to activation of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in rabbits anesthetized with chloralose. Baroreceptor activity was measured during ramp or step increases in nonpulsatile carotid sinus pressure over a range of 0–175 mm Hg. Exposure of the isolated carotid sinus to inhibitors of prostaglandin formation (indomethacin [n= 10] or aspirin [n=6]) decreased baroreceptor activity significantly (p<0.05). The slope of the pressure-activity relation averaged 0.80±0.07 %/mm Hg (mean±SEM) during control measurements and 0.72±0.06 and 0.63±0.05 %/mm Hg during exposure to 10 and 20 μM indomethacin, respectively. Exposure of the carotid sinus to exogenous prostacyclin (PGI2[n=11]) increased baroreceptor activity significantly. The slope of the pressure-activity relation averaged 0.89±0.10, 1.09±0.09, and 1.26±0.16 %/mm Hg during control and during exposure to 10 and 20 μM PGI2, respectively. Activity returned to control after removal of PGI2(0.89±0.12 %/mm Hg). Removal of endothelium with either a balloon catheter (n=4) or a jet of a 95% O2-5% CO2gas mixture (n=6) decreased the slope of the pressure-activity relation from 0.92±0.09 to 0.56±0.08 %/mm Hg (p<0.05). Exposure of the denuded sinus to exogenous PGI2(20 μM [n=4]) restored activity (slope=1.09±0.24 %/mmHg). Neither indomethacin (n=5) nor PGI2(n=5) nor denudation (n=5) significantly altered the pressure-diameter relation of the carotid sinus (sonomicrometers), suggesting that the effects on baroreceptor discharge are not caused by altered stretch of the carotid sinus at a given pressure. The results suggest that prostaglandins (e.g., PGI2) released from endothelium contribute in a paracrine manner to activation of baroreceptors during increases in arterial pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1990

数据来源: OVID