摘要:

To clarify the role of renal prostanoid in hyperreninemia and high blood pressure in human renovascular hypertension, we measured prostaglandin E2and renin activity in renal venous and abdominal aortic plasma before and after the intravenous administration of the cyclooxygenase inhibitor, aspirin DL-lysine. Subjects were six patients with unilateral renovascular hypertension and six with essential hypertension. In patients with renovascular hypertension, prostaglandin E2concentration in renal venous plasma from the stenotic kidney was 9.25 ±1.48 pg/ml, which was significantly higher (p< 0.01) than the concentration in the renal venous plasma from the normal kidney (4.97±1.02 pg/ml) or in the aortic plasma (2.59±0.15 pg/ml). Plasma renin activity was also higher in the renal vein of the stenotic kidney than in the other two sites. The stenotic side/normal side ratio of the renal venous prostaglandin E2correlated significantly with a renin ratio greater than 1.5 (r=0.8211,p< 0.05). Intravenous injection of aspirin DL-lysine (18 mg/kg) 30 minutes later markedly suppressed prostaglandin E2and renin levels at all sites and clearly lowered arterial blood pressure (mean: from 120±6 to 110±5 mm Hg,p< 0.01). The reduction in blood pressure correlated significantly with the suppression of plasma renin activity in the aorta (p< 0.05) and in the renal vein of the stenotic kidney (p< 0.01). Conversely, in patients with essential hypertension, aspirin had little effect on renin levels and increased mean blood pressure. These data indicate that renal prostaglandin plays an important role in the augmented release of renal renin and the pathogenesis of hypertension in human renovascular hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The role of several factors that have been suggested as being of etiologic importance in renovascular fibromuscular dysplasia was examined in a case-control study of 33 patients with angiographically demonstrated fibromuscular dysplasia and 61 renal transplant donor control subjects with normal renal arteries. The factors studied included use of oral contraceptive agents or markers of sex hormone dysfunction, mechanical stress to the renal artery wall, human lymphocytic antigen (HLA) type, cigarette smoking, history of hypertension for more than 5 years, and family history of cardiovascular disease. The risk of fibromuscular dysplasia was significantly (p< =0.003) increased (odds ratio=4.1, 95% confidence interval=1.5–10.9) among cigarette smokers. A significant (/x 0.001) dose-response relation was noted between cigarette use and the risk of fibromuscular dysplasia developing (odds ratio=8.6 for those who had smoked more than 10 pack-years). Personal history of hypertension more than 5 years was also associated (odds ratio=5.0,95% confidence interval=1.1–22.8) with a significantly (p= 0.036) increased risk for the development of fibromuscular dysplasia. HLA-DRw6 antigen was more common in the 33 fibromuscular dysplasia patients than in the 61 renal transplant donor control subjects (odds ratio=3.00,p< =0.067) or a second group of 934 ambulatory control subjects (odds ratio=2.51,p= 0.03l). Adjustment for cigarette smoking increased the odds ratio to 5.0 (95% confidence interval=1.3–19.6). There was a positive though not statistically significant (odds ratio=1.7,p= 0.175) association noted between family history of cardiovascular disease and fibromuscular dysplasia. No evidence of an etiologic association between the occurrence of fibromuscular dysplasia and prior oral contraceptive use, endogenous sex hormone abnormality, or increase in renal mobility was noted. Our results suggest that cigarette smoking and genetic predisposition are of etiologic importance in fibromuscular dysplasia. However, they fail to support the putative role of other previously suggested causal factors such as oral contraceptive use and excessive renal mobility.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1,1, 4, 16, and 32 jug/kg/min for 10 minutes. At all doses greater than 0.1 /μg/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 Aig/kg/min, which reduced MAP by an average of 15.8±1.4 mm Hg (n=14) and plasma renin activity and plasma Ang II concentration to 3% (n=9) and 15% (n=5), respectively, of the pretreatment values. At 0.1 /tμ/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n=3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 /i.g/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 ±2.4 mm Hg (n=10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80–160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8±5.4 mm Hg (n=4) above the mean pretreatment value. Similar injection under the influence of captopril had no pressor effect. Injection of purified human renin (0.01–0.02 Goldblatt units/kg/min i.v.) into sodium-replete monkeys raised the MAP by an average of 36.5 mm Hg (n=2). Simultaneous intravenous infusion of R-Pep-27 at 100 jLtg/kg/min for 8–12 minutes caused the elevated MAP to return to normal. This study reveals the effects of blockade of circulating renin in a conscious primate model and suggests that R-Pep-27 will find use as a clinical tool in investigations of the role of renin in essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A specific angiotensin II monoclonal antibody, KAA8, was used to examine the interaction between sympathetic function and angiotensin II in pithed rats. KAA8, at 5 or 50 nig/kg i.v., did not alter the mean blood pressure, cardiac output, total peripheral resistance, or heart rate responses to sympathetic neural stimulation (0.25–4.0 Hz) or to norepinephrine (0.3–3 /μg/kg i.v.) but blocked significantly the hemodynamic responses to angiotensin II (0.03–1.0 /ig/kg i.v.) and to angiotensin III (0.3–10 /u-g/kg i.v.). KAA8 treatment also reduced the plasma immunoreactive angiotensin II from 2,880±475 pg/ml to an undetectable level. In contrast, captopril (5 mg/kg i.v.) and saralasin (10 or 50 ju.g/kg/min i.v.) inhibited the mean blood pressure and total peripheral resistance responses, but not the cardiac output and heart rate responses, to sympathetic neural stimulation and to norepinephrine. These results, which confirm previous findings by Kaufman and Vollmer (Kaufman LJ, Vollmer RR: Endogenous angiotensin II facilitates sympathetically mediated hemodynamic responses in pithed rats. J Pharmacol Exp Ther 1985;235:128–134), demonstrate that angiotensin II selectively potentiates the sympathetic vascular function in the pithed rat. However, our results suggest that circulating angiotensin II does not appear to interact with the sympathetic vascular function. It is speculated that in the pithed rat the sympathetic vascular response is enhanced by vascular-formed angiotensin II.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The mechanisms of increased arterial pressure lability after sinoaortic deafferentation remain unknown. We have shown previously in rats with chronic sinoaortic deafferentation (7–14 days after sinoaortic deafferentation) that ganglionic blockade significantly reduced mean arterial pressure and arterial pressure lability. The present study investigated the possibility that lability is related to the level of arterial pressure. Rats were instrumented chronically and heart rate and mean arterial pressure were sampled every 5 seconds in the conscious, freely moving state. Graded sustained increases in pressure (+10 to +82 mm Hg) produced by constant infusion of angiotensin II, phenylephrine, or vasopressin did not affect lability (standard deviation of 30-minute sampling period); whereas, graded hypotension (−10 to −70 mm Hg) produced by infusions of adenosine, nitroprusside, or nisoldipine appeared to reduce lability. Analysis of covariance and orthogonal polynomial curve fitting demonstrated a significant correlation between the decrease in mean arterial pressure and the decrease in lability produced by nisoldipine but not by adenosine or nitroprusside. Lability does not appear to be solely dependent on the level of arterial pressure because lability was reduced by adenosine when pressure was maintained at control levels by simultaneous infusion of phenylephrine. We conclude that 1) arterial pressure lability is not influenced by elevation of arterial pressure but can be reduced when pressure is lowered by certain vasodilators and 2) pressure alone does not appear to be the major determinant of lability because it can be attenuated by vascular smooth muscle relaxants even when pressure is maintained.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Microneurographic recordings of muscle nerve sympathetic activity, which is governed by baroreceptors and involved in blood pressure regulation, were made in the peroneal nerve in 16 healthy volunteers during physiological bladder distension. When the urge to urinate was pronounced, sympathetic outflow increased from a baseline level of 16.3±1.7 to 23.2±1.9 bursts/min (mean ±SEM,p< 0.01). There was a concomitant significant rise in both systolic and diastolic blood pressure, from 125±2/74±2 to 140±4/84±3 mm Hg. After micturition, sympathetic activity and blood pressure returned toward initial values. It is concluded that 1) increased sympathetic outflow contributed to the rise in blood pressure, 2) there is a vesicovascular response mediated by sympathetic vasoconstrictor neurons in humans corresponding to mechanisms observed in animals, and 3) the described functional relation between bladder distension and sympathetic vasoconstrictor activity probably plays a role in clinical conditions such as autonomic dysreflexia in humans with cervical spinal cord lesions and nocturnal micturition syncope.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Abnormal baroreceptor reflex function that antedates or is a consequence of NaCl loading could contribute to the NaCI-induced exacerbation of hypertension in NaCI-sensitive spontaneously hypertensive rats (SHR-S). The current study tested the hypothesis that an impairment in cardiopulmonary baroreceptor reflex function exists in SHR-S before NaCl loading. The reflex response to volume expansion was compared in SHR-S, NaCI-resistant SHR (SHR-R), and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats maintained on a normal NaCl diet. Conscious, free-moving SHR-S, SHR-R, WKY, and Sprague-Dawley rats were volume expanded with whole blood to 15% of blood volume within 6 minutes, and mean arterial pressure, heart rate, and lumbar sympathetic nerve activity were recorded. Heart rate and lumbar sympathetic nerve activity decreased significantly in SHR-R, WKY, and Sprague- Dawley rats after volume expansion. In contrast, in SHR-S neither heart rate after volume expansion nor lumbar sympathetic nerve activity was significantly different from levels before volume expansion. The blunted reflex response of heart rate and lumbar sympathetic nerve activity to volume expansion suggests impaired cardiopulmonary volume receptor function in SHR-S. This likely contributes to NaCI-induced hypertension in SHR-S on a high NaCl diet.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Cardiovascular reactivity to stress is hypothesized to be a marker for subsequent neurogenic cardiovascular disease, but few prospective studies of this hypothesis are available. We studied 910 white male medical students who had their blood pressure and pulse rate measured before and during a cold pressor test in the years 1948–1964. Hypertensive status (requiring drug treatment) was ascertained by annual questionnaires in the 20- to 36-year follow-up period. An association was observed between maximum change in systolic blood pressure and later hypertension, with a cumulative incidence of hypertension by age 44 of 6.7%, 3.0%, and 2.4% for a change in systolic blood pressure in the upper, middle two, and lowest quartiles, respectively (Kaplan-Meier,p< 0.02). After adjustment for study entry age, Quetelet Index, cigarette smoking, pretest systolic blood pressure, and paternal or maternal history of hypertension in a Cox model, the association persisted. The excess risk associated with systolic blood pressure reactivity was not apparent until the population aged some 20 years and was most apparent among those in whom hypertension developed before age 45 (relative risk=2.5, 95% confidence intervals=1.47, 4.71 for a 20 mm Hg change). Diastolic blood pressure and heart rate changes were not associated with later hypertension. These data suggest that persons prone to later hypertension manifest an altered physiology at a young age.

ISSN:0194-911X    

出版商:OVID    

年代:1989

数据来源: OVID