摘要:

In rat cerebral microvessels, we characterized α1- and α2-adrenergic receptors, using [3H]prazosin and [3H]-p-amino-clonidine as radioligands. [3H]Prazosin binding to the cerebral microvessels was saturable and of high affinity (dissociation constant of 78 pM), with a maximum binding of 48 fmol/mg protein. [3H]Prazosin binding reached equilibrium within 15 minutes and was dissociated by the addition of 10 μ phentolamine. The inhibitory effects of isomers of norepinephrine and epinephrine on the binding showed thatl-isomers were over 10 times more potent thand-isomers. [3H]-p-Amino-clonidine binding to the cerebral microvessels was saturable and of high affinity (KD = 0.61 nm) with a Bmax, of 73 fmol/mg protein. The binding reached equilibrium within 30 minutes, and was dissociated by the addition of 100 μml-norepinephrine.l-Isomers of norepinephrine and epinephrine were over 10 times more potent thand-isomers in displacing the binding. Thus, both [3H]prazosin and [3H]-p-amino-clonidine bindings to the cerebral microvessels were characterized by saturability, high affinity, reversibility, and stereo-specificity. Furthermore, the specificity of both binding sites was pharmacologically evaluated by the inhibitory effects of various adrenergic agonists and antagonists on the bindings. These data indicate the existence of α-adrenergic receptors in the cerebral microvessels and are consistent with the hypothesis that the cerebral microcirculation is regulated by adrenergic innervation. Furthermore, the receptors were measured in cerebral microvessels of spontaneously hypertensive rats and Wistar-Kyoto controls. The number of α1-receptors in the cerebral microvessels of spontaneously hypertensive rats was significantly higher than that of Wistar-Kyoto rats, without any difference in the affinity constant to the ligands. No difference in α2-receptors was observed between spontaneously hypertensive and Wistar-Kyoto rats. These results suggest that the neuronal regulatory mechanisms of the cerebral microcirculation are altered in hypertension.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

This study compares the effect of arginine-vasopressin with phenylephrine on arterial pressure, heart rate, and renal sympathetic nerve activity in conscious rabbits with and without functional arterial baroreflexes and in rabbits with lesions of the area postrema. In intact rabbits, progressive infusions of arginine-vasopressin result in large decreases in renal sympathetic nerve activity and heart rate for a given increase in blood pressure as compared to progressive infusions of phenylephrine. In sinoaortic-denervated rabbits, the responses of arterial pressure on heart rate and renal sympathetic nerve activity to both arginine-vasopressin and phenylephrine are markedly attenuated, indicating the necessity for afferent baroreceptor activity in this response. This observation indicates that arginine-vasopressin is acting centrally to enhance the baroreflex. A central site of action of circulating vasopressin may be the area postrema, since it is the only circumventricular organ in the hindbrain. Lesioning the region of the area postrema resulted in a normalization of the responses evoked with arginine-vasopressin and phenylephrine. There was no difference in the phenylephrine responses of arterial pressure on renal sympathetic nerve activity or heart rate in area postrema-lesioned animals, compared to control rabbits. Therefore, we conclude that the area postrema or its surrounding tissue is either a site of action of circulating arginine-vasopressin or contains fibers of passage from another site where arginine-vasopressin acts to enhance baroreflex activity.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Somatomedin-C, a peptide growth factor that is also termed insulin-like growth factor 1, stimulates smooth muscle cell replication; however, these cells proliferate in somatomedin-C-defitient medium. We postulated, therefore, that these cells might release a somatomedin-like molecule into the surrounding culture medium. Porcine aortic smooth muscle cells that were exposed to serum-free Dulbecco's modified minimum essential medium for 24 hours were found to release a somatomedin-like molecule that could be detected by a specific radioimmunoassay for somatomedin-C. Several variables in the design of tissue culture conditions were found to regulate the secretion of the somatomedin-like peptide. There was an inverse relationship between somatomedin-like peptide secretion and culture density. Cultures grown to a density of 110,000 cells/well secreted 0.18 ± 0.02 U/ml per 105 cells, whereas cultures grown to 38,000 cells/well secreted 0.59 ± 0.06 U/ml per 105 cells (P< 0.001). Serum deprivation and days of preincubation before initiation of an experiment were found to influence somatomedin-like peptide secretion significantly. Platelet-derived growth factor, which stimulates smooth muscle cell replication, was a potent stimulant of somatomedin-like peptide secretion. Exposure to a concentration of 500 ng/ml platelet-derived growth factor induced a 2.8-fold increase in somatomedin-like peptide secretion over basal levels, (i.e., 0.37 ± 0.05 to 0.98 ± 0.7 U/ml,P< 0.001). The effect of platelet-derived growth factor was enhanced (41% increase) by concomitant incubation with 1% soma- tomedin-C-deficient platelet poor plasma. Transient exposure to platelet-derived growth factor followed by exposure to 1% somatomedin-C-deficient platelet-poor plasma caused a sustained increase in somatomedin-like peptide production even after platelet-derived growth factor had been removed from the culture dish. In contrast to platelet-derived growth factor, hormones and growth factors that circulate in plasma and do not stimulate smooth muscle cell replication after transient exposure, did not stimulate quiescent cultures to secrete the somatomedin-like peptide. However, if the cultures were transiently exposed to platelet-derived growth factor, then exposed to either insulin, epidermal growth factor, or thyroxine, each stimulated somatomedin secretion. Since these hormones were inactive when added to quiescent cultures, it is postulated that entry into the cell cycle is required to achieve stimulation with these substances. The production of this somatomedin-like peptide may be linked to smooth muscle cell replication, since many factors which stimulate replication also facilitate production and release of this material.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

We investigated the role of altered vascular calcium handling in the development of aldosterone-salt hypertension in the rat. The calcium sensitivity of isometric force in response to 50 mm KCl was compared in aortic rings from control and aldosterone-hypertensive rats. Over the entire range of calcium concentrations studied, responses in aortas from the hypertensives were significantly depressed compared to controls [ED50: aldosterone-hypertensive rats (n= 6), 0.739 ± 0.137; controls (n= 7), 0.141 ± 0.021 mm; P < 0.001]. However, calcium sensitivity in response to 1 μm norepinephrine was similar in aortas from both hypertensives and controls [ED50: aldosterone-hypertensive rats (n= 7), 0.196 ± 0.022; controls (n= 7), 0.180 ± 0.024 mm]. The calcium sensitivity of Triton ±-100 skinned aortic rings from aldosterone-hypertensive rats was likewise not significantly different from sensitivity in controls [ED50: aldosterone-hypertensive rats (n= 9), 3.61 ± 10–7 ±0.57; controls (n= 8), 3.89 ± 10–7 ± 0.64 m]. Therefore, the observed decrease in calcium sensitivity in response to membrane depolarization in aortas from aldosterone-hypertensive rats probably is not due to a change in calcium sensitivity of the contractile system itself. The time course for development of changes in calcium handling in vessels from the aldosterone-hypertensive rats was found to be quite different from the time course for changes in monovalent ion metabolism. Whereas increases in monovalent ion permeability reportedly appear as early as one week after the start of aldosterone-salt treatment, significant alterations in calcium handling were not apparent until after four weeks of treatment. After one week of aldosterone-salt treatment, calcium sensitivity in response to 50 mM KCl was similar in aortas from the aldosterone-treated rats compared to controls. After two weeks, the ED50 for calcium sensitivity in response to 50 mM KCl was slightly increased in the aldosterone-treated group, compared to controls. Therefore, the trend appears to be a progressive decrease in calcium sensitivity in aortic smooth muscle during the development of aldosterone-salt hypertension in the rat. This reduction in calcium sensitivity appears to be primarily a membrane phenomenon; it is unlikely that it reflect alterations in the contractile system itself.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Structural and electrophysiological properties of the epicardial muscle which survives on the surface of transmural infarcts of the canine heart (epicardial border zone) were studied at different times after occlusion of the left anterior coronary artery (LAD). Isolated preparations were superfused in vitro, transmembrane potentials recorded, and impulse propagation mapped. In preparations from subacute infarcts (1 and 5 days), resting potential, action potential amplitude, upstroke velocity, and duration were all significantly reduced. Well-defined directional differences in propagation occurred. Propagation was more rapid in the direction perpendicular to the left anterior coronary artery than in the direction perpendicular to the base of the heart, because of the uniform anisotropic structure of the surviving muscle fibers which were arranged in tightly packed bundles oriented perpendicular to the left anterior coronary artery. The only ultrastructural abnormalities found in these muscle fibers was an accumulation of large amounts of lipid droplets. As the infarcts healed, resting potential, action potential amplitude, and upstroke velocity returned to normal by 2 weeks, although action potential duration decreased further. Lipid droplets had disappeared, and connective tissue had invaded the epicardial border zone, separating the muscle bundles. By 2 months, action potentials were normal, but the muscle fibers were widely separated and disoriented by the connective tissue (parallel bundles no longer were found). In these regions with a nonuniform anisotropic structure, the well-defined directional differences in impulse propagation were lost. However, activation was very slow, perhaps because of diminished connections between cells. The persistence of slow conduction in healed infarcts may contribute to the occurrence of chronic arrhythmias.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Prolonged exposure to high concentrations of strophanthidin produces an initial increase followed by a subsequent decrease of twitch tension. The slow decrease is termed calcium overload. The aim of the present work was to investigate the effects of ryanodine (an inhibitor of calcium release from the sarcoplasmic reticulum) on calcium-overloaded sheep cardiac Purkinje fibers. The fibers were voltage-clamped, and tension was measured while monitoring the intracellular calcium concentration with the photoprotein aequorin. When strophanthidin (10 μM) was applied to produce calcium overload, a depolarizing pulse produced twitch, and tonic components of tension and repolarization produced an aftercontraction. These components of tension were accompanied by corresponding increases of aequorin light. Ryanodine (1 μM) gave a transient increase of twitch tension. The twitch then decreased to very low levels. The aftercontraction and its corresponding aequorin light signal decreased monotonically on application of ryanodine. It has been suggested that the fall of force in calcium overload may be due to random diastolic release of calcium from the sarcoplasmic reticulum interfering with subsequent systolic calcium release. We suggest that the positive inotropic effect of ryanodine can be explained if ryanodine decreases the diastolic release of calcium. The transient positive inotropic effect of ryanodine reported here is therefore consistent with the hypothesis that the fall of force in calcium overload is due to diastolic calcium oscillations.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Plasma norepinephrine concentrations are elevated in patients with decompensated cirrhosis, and correlate inversely with urinary sodium and water excretion. Increased plasma norepinephrine concentrations may result from a decreased metabolic clearance rate or an increased secretion rate, possibly in response to a decreased effective arterial blood volume. If the latter hypothesis is correct, plasma norepinephrine might be expected to be suppressed when central blood volume is expanded by head-out water immersion. In the present study, plasma norepinephrine secretion and clearance rates were determined by infusion of tritiated norepinephrine. Norepinephrine secretion rates were elevated in eight cirrhotic patients as compared to control subjects (1.50 ± 0.25 vs. 0.26 ± 0.08 μg/m2per min, P < 0.001), whereas clearance rates were similar (3.13 ± 0.48 vs. 2.60 ± 0.28 liters/min, NS). Baseline plasma norepinephrine concentrations were markedly elevated in the cirrhotic patients (830 ± 136 vs. 185 ± 12 pg/ml, P < 0.001). Head-out water immersion significantly suppressed plasma concentrations of both norepinephrine (704 ± 72 to 475 ± 70 pg/ml, P < 0.005) and epinephrine (121 ± 33 to 57 ± 10 pg/ml, P < 0.05) in all seven patients studied. We conclude that the high circulating catecholamine concentrations in cirrhosis are secondary to increased secretion, rather than to decreased metabolic clearance, and are suppressible by central blood volume expansion.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

The purpose of this study was to examine the contribution of the subfornical organ to the chronic hypertension produced by intravenous angiotensin II infusion in rats. Male rats were instrumented with permanent arterial and venous catheters and housed in metabolism cages for daily measurement of arterial pressure, heart rate, water intake, water balance, and urinary electrolyte excretion. Angiotensin II was infused intravenously at a rate of 10 ng/minute for 5 consecutive days, preceded by 2 control days, and followed by 2 recovery days. Normal rats with an intact subfornical organ (n = 7), and rats with an electrolytic lesion placed such that greater than 80% of the subfornical organ was destroyed (n = 9), were studied using this infusion protocol. An additional group of eight rats did not receive angiotensin II, and, thus, served as a time control. Both groups of rats receiving angiotensin II exhibited significant elevations in arterial pressure during the 5-day hormone infusion period, but pressure in rats with subfornical organ lesions (A23–29 mm Hg) was increased significantly more than that of intact rats (A14–20 mm Hg). Water intake was significantly increased on the 3rd, 4th, and 5th days of angiotensin II infusion only in rats with lesions in the subfornical organ. In contrast to previous studies showing that an intact subfornical organ is required for normal pressor and drinking responses to acute elevations in circulating angiotensin II in the rat, the current experiments indicate that the presence of the subfornical organ actually inhibits these same responses during more chronic increases in plasma angiotensin II levels.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID