ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Angiotensin II has recently been shown to exert potent control over sodium and water absorption in the proximal convoluted tubule. This transport stimulation is effected by receptors on both the luminal and basolateral membranes of cells located predominantly in the early, S, proximal tubule. Angiotensin II increases transport primarily by a Gf proteinmediated reduction in intracellular cyclic adenosine monophosphate, which enhances the affinity of the Na+-H+antiporter. Change in early proximal acidification ultimately causes alteration in the amount of sodium chloride leaving the proximal tubule and entering the urine. These direct tubular transport actions by angiotensin II may participate importantly in various physiological actions of the kidney, including the renal response to change in dietary sodium intake and in extracellular volume, as well as in pathophysiological processes such as hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In conscious 18–21-week-old spontaneously hypertensive rats, DuP 753, a nonpeptide angiotensin II receptor antagonist, given orally at 3 and 10 mg/kg or intravenously at 3,10, and 30 ing/kg, reduced blood pressure dose dependently. It did not alter heart rate at these doses. At 10 mg/kg i.v., DuP 753 decreased blood pressure significantly for at least 24 hours, suggesting a long duration of the antihypertensive effect. Unlike saralasin, DuP 753 did not cause a transient increase in blood pressure. The acute antihypertensive efficacy of DuP 753 was greater than that of captopril. Our data indicate that, for captopril to reduce blood pressure to a similar extent as that of DuP 753, it would need to be supplemented by a diuretic. DuP 753 did not have an acute diuretic effect. Bilateral nephrectomy, but not inhibition of prostaglandin synthesis, abolished the antihypertensive effect of DuP 753, suggesting that the antihypertensive effect of DuP 753 is dependent on an active renin-angiotensin system. Furthermore, DuP 753 inhibited the pressor response to angiotensin II but not the responses to norepinephrine, vasopressin, and Bay K 8644 (a calcium agonist). As neither DuP 753 nor captopril decreased blood pressure acutely in Wistar-Kyoto normotensive rats, our results suggest that the renin-angiotensin system plays a significant role in the control of blood pressure in spontaneously hypertensive rats.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The possibility that prostacyclin or thromboxane biosynthesis is abnormal in patients with established mild essential hypertension was investigated in 46 patients. These eicosanoids have opposing effects both on vascular smooth muscle and on platelets. An imbalance in their biosynthesis could therefore influence both vascular tone and predisposition to thrombosis. We studied the relation between blood pressure and the biosynthesis of prostacyclin and thromboxane A2by measuring urinary excretion rates of stable breakdown products of prostacyclin (6-oxo-prostaglandin F1α and 2,3-dinor-6-oxo-prostaglandin F,J and of thromboxane A2(thromboxane B2and 2,3-dinor-thromboxane B2) using immunoafnnity chromatography and gas chromatography/electron capture mass spectrometry. Excretion rates of both of the prostacyclin-derived products ranged from less than 5 to more than 100 ng/g creatinine; each was significantly negatively correlated with blood pressure (r= 0.36–0.45). A reduction of 2,3-dinor-6-oxo-prostaglandin F,a excretion of 100 ng/g creatinine was associated with an increase in arterial pressure of 14 mm Hg (systolic) and 8 mm Hg (diastolic) in patients who had been without antihypertensive medication for 2 weeks. The same reduction in 6- oxo-prostaglandin Fla excretion was associated with an increased pressure of 19 mm Hg (systolic) and 12 mm Hg (diastolic) (2p< 0.05 for diastolic pressure and 2p< 0.01 for systolic pressure in each case). There were similar correlations between the excretion rates of these products and blood pressure in the same patients while they were receiving antihypertensive therapy. In contrast, excretion rates of thromboxane B2and 2,3-dinor-thromboxane B2were not significantly correlated with blood pressure. We conclude that prostacyclin biosynthesis is selectively impaired in mild essential hypertension. This could contribute to the raised peripheral resistance and increased incidence of thrombosis that are characteristic of essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The rings of the thoracic aorta were obtained from age-matched SHR and WKY rats, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the aortic rings from SHR were significantly weaker than those from WKY rats. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase inhibitor (indomethacin) or thromboxane A2/ prostaglandin H2receptor antagonist (ONO-3708) in aortic rings from both SHR and WKY rats. A thromboxane A2 synthetase inhibitor (OKY-046) did not affect the acetylcholineinduced relaxation in the aortic rings from SHR or WKY rats. In the organ bath solution, after acetylcholine stimulation, prostaglandin E2 and 6-keto-prostaglandin Fla concentrations increased but not prostaglandin F2a and thromboxane B2concentrations. Exogenous prostaglandin H2, a stable analogue of thromboxane A2, and prostaglandin F2α induced contractions of the SHR rings at a lower concentration than prostaglandin E2, prostaglandin D2, and prostaglandin I2. These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endotheliumderived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in those of WKY rats and suggest that prostaglandin H2, a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The regional hemodynamic consequences of inhibiting vascular endothelial nitric oxide generation withNG-monomethyl-L-arginine (L-NMMA) were studied in conscious Long-Evans rats. Experiments were carried out in groups of chronically instrumented rats with intravascular catheters and pulsed Doppler probes to monitor regional blood flow. L-NMMA (0.3–300 mg/kg) caused a dose-dependent, long-lasting (5–90 minutes), and enantiomerically specific increase in mean blood pressure and also caused bradycardia. The increase in blood pressure was accompanied by a dose-dependent and long-lasting vasoconstriction in the internal carotid, mesenteric, renal, and hindquarters vascular beds that could be attenuated, in a concentrationdependent manner, by L-arginine but not by D-arginine. In contrast, L-arginine did not affect the pressor or vasoconstrictor effects of vasopressin. These results indicate that nitric oxide production by vascular endothelial cells contributes to the maintenance of blood pressure and to the control of the resting tone of different vascular beds in the conscious rat.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Endothelin-l is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-l, plasma levels of immunoreactive endothelin- I were measured in 32 research subjects with normal renal function (21 normal subjects and II patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-l levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-l levels than normal subjects (2.29±1.09 vs. 1.41±0.50 pg/ml, p<0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n=17) had higher plasma endothelin-l levels than the comparable normotensive group (n=7) (3.08±3.43 vs. 0.73±0.34 pg/ml, p<0.05), and the hemodialyzed hypertensive group (n=18) had higher plasma endothelin-l levels than the comparable normotensive group (n=33) (2.66±1.92 vs. 1.35±0.73 pg/ml, p<0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-l levels. These data suggest that circulating endothelin-l may be partly involved in the development or maintenance of hypertension in humans.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The purpose of this study was to determine if the arterial baroreceptor reflexes modulate the sympathocirculatory responses to acute heat stress. To address this, arterial pressure, heart rate, mesenteric and renal blood flow velocity (Doppler flow probes), arterial plasma norepinephrine, and colonic temperature were measured before and during whole body heating (42° C ambient temperature) in groups of conscious, unrestrained rats with (sham) or without (sinoaortic deafferentation) intact arterial baroreceptor reflexes. Heating was stopped when a colonic temperature of 41° C was attained. Baseline levels of arterial pressure were similar in the two groups, whereas heart rate was elevated in deafferented versus sham-operated rats (p<0.01). The increases above baseline for both arterial pressure (73±4 vs. 27±2 mm Hg) and heart rate (127±10 vs. 33±5 beats/min) were threefold to fourfold greater at the end of heating in the deafferented versus the sham group (/7<0.01). Declines in mesenteric and renal blood flow were similar in the two groups during heating; however, deafferented rats had greater increases in both mesenteric and renal vascular resistance (p<0.05). Plasma norepinephrine was elevated at baseline in deafferented versus sham rats and increased in both groups during heating (/?<0.01). The magnitude of the increase in plasma norepinephrine from baseline to 41° C was fivefold greater in the deafferented versus the sham rats (p<0.01). Furthermore, deafferented rats reached a colonic temperature of 41° C much faster than the sham rats (38±6 vs. 94±13 minutes), resulting in a threefold greater heating rate (p<0.01). These findings indicate that the arterial baroreceptors modulate the arterial pressure, heart rate, and visceral vascular resistance responses to nonexertional heat stress in the conscious rat and suggest that this modulation is mediated, at least in part, via baroreceptor inhibition of central sympathetic outflow. Moreover, thermal tolerance during prolonged heat exposure is in part dependent on intact arterial baroreceptor reflexes.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID