摘要:

Low doses (1–10 ng) of angiotensin I (AI) injected Intravenously into conscious rats produced greater pressure changes than when injected intraaortically. This finding again indicates the importance of the pulmonary circulation in the conversion of AI to angiotensin II (All). At high doses of hormone (30 ng, which produces pressure rises of 40–50 mm Hg) the Intravenous and intraarterial responses tended to be the same. However, the role of the lung for conversion is still indicated by comparing the time for onset of the pressure rise and the time to reach maximum pressure rise for the intravenous and intraarterial injection of AI. Bradykinin degradation in the pulmonary circulation, estimated by comparing intravenous and intraaortic equipressor doses, was higher in conscious rats with chronic onehyphenkklney renal hypertension (RHR; 217 ± 3 mm Hg) than in the normotensive control rats (NCR; 126 ± 3 mm Hg), 99.6% and 97.5%, respectively. Vascular hyperreactivity to bradykinin was seen in RHR in response to both intraaortic bolus injection and intraaortic infusion. The intraaortic equipressor dose was 15–30 times smaller In RHR than in NCR, while the differences with Isoproterenol and nitropnisside were less pronounced. Indomethacin infusion (5 mg/kg/min) for 10 minutes had no effect on intraarterial hyperreactivity to bradykinin. The marked increase in vascular reactivity to bradykinin more than compensated for the larger pulmonary Inactivation. The equipressor doses of bradykinin injected intravenously were 200 ± 24 ng in RHR and 1060 ± 143 ng in NCR. Conversion AI to AH, assessed by the equipressor doses of the hormones which produce 20 mm Hg rise in pressure, was also higher in the RHR than in the NCR, 55% vs 25%, with no change in vascular reactivity to AH. Hyperreactivity to bradykinin reverted entirely to normal 20 hours after unclipping the RHR, when blood pressure had also normalized. The responsiveness to nitroprusside tended to increase rather than decrease after unclipping. While the vascular hyperreactivity to bradykinin and the increased pulmonary degradation of bradykinin seen in the RHR were markedly affected by unclipping, the increased conversion of AI to AH and reactivity to AH remained unchanged after unclipping. These results suggest that the mechanism underlying the alterations in AI conversion and bradykinin degradation in onehyphenkidney renal hypertensive rats can be partially dissociated. (Hypertension 4: 77–83, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Distinct bemodynamic and volume characteristics have been suggested for established hypertension in severe obesity, namely, a high cardiac output, an expanded blood volume, and a normal peripheral resistance. To evaluate whether hypertension in moderately obese patients represents a separate entity that can be defined by hemodynamic and volume profiles, we studied these in 50 such patients and compared results with those obtained in 59 nonobese essential hypertensives and 25 normal subjects. Both obese and nonobese hypertensives had a normal cardiac index (men, 2.8 ± 0.1 vs 2.8 ± 0.09 llter/mln/m2; women, 2.9 ± 0.1 vs 2.8 ± 0.1 liter/min/m2, respectively) and similarly elevated total peripheral resistance (men, 47.1 ± 2.3 vs 46.5 ± 1.9 U·m2women, 45.0 ± 2.4 vs 44.0 ± 1 3 U·m2, respectively) as compared to normals (cardiac index: men, 2.9 ± 0.09 liter/min/m2, women, 3.4 ± 0.2 liter/min/m2; total peripheral resistance: men, 29.4 ± 1.0 U·m2, women, 28.3 ± 2.8 U·m2). Volume measurements corrected to body surface area snowed that both obese and nonobese hypertensive patients had lower blood volume (men, 2.6 ± 0.05 vs 2.5 ± 0.05 liter/m2; women, 2.2 ± 0.05 vs 2.5 ± 0.05 liter/m2, respectively) than normals (men, 2.9 ± 0.08 liter/m*; women, 2.5 ± 0.08 liter/m2). The results of this study suggest that hypertension in moderately obese subjects is similar in its bemodynamic and volume profiles to hypertension in the nonobese and that the presence of obesity does not alter the hemodynamic characteristics of established essential hypertension. (Hypertension 4: 84–92, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Prazosin was administered to 16 patients with essential hypertension in an initial dose of 0.5 mg, after which the blood pressure (BP), pulse, and plasma concentrations of prazosin were measured at 0,0.5, 1,1.5, 2,2.5, 3, 4, 6, 8, and 24 hours. The dose of prazosin was then increased over 16 to 20 weeks, and similar sequences of measurements were obtained twice. Eleren patients completed the 20-week course. All patients did not respond in a similar way; two distinct patterns of BP and poise response emerged, although there was no significant difference in the pharmacoklnetic parameters, namely, absorption rate constant (Ka), maximum plasma concentration (Cpmax), time to reach the maximum concentration (Tmax), prazosin plasma halflife (T 1/2 ), elimination rate constant (kel), prazosin plasma concentrationhyphentime curre (AUC), and clearance. Patients in Group 1 had a marked reduction (52/30 ram Hg) of BP after the first dose of prazosin, no pulse increase, and needed a small dose of prazosin to maintain an adequate BP response. Patients in Group 3 had a minimal reduction in BP (14/13 mm Hg) after a first dose, a significant pulse increase, and needed a high dose of prazosin to control their BP. We conclude that this effect might be due to a different drughyphenreceptor interaction, and the BP response and dose could be predicted from the response of the first dose of prazosin. (Hypertension 4: 93–101, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Various facets of activation of inactive renin by addification or cold exposure were investigated in normal human plasma. The add activation obtained by titration was usually less than that by dialysis method, but varied from 41% to 122% of the latter. The add phase of add activation accounted for about 70% of tbe total activation achieved by the combined effects of the add and alkaline phases on the average, and was not affected by any of the inhibitors for serine, thiol or carboxyl protease, whereas serine protease inhibitors suppressed the activation of both renin and plasma kallikrein in tbe alkaline phase of acid activation. A different mode of plasma kallikrein activation suggested some difference in the mechanism between the alkaline phase of acid activation and tbe cryoactivation. A part of cryoactivation of renin was independent of the action of plasma kallikrein. Tbe renin activated by either addification or cold exposure without concomitant activation of plasma kallikrein was reinactivated by tbe reversal of pH and temperature, but recovered by repeating acidification or cold exposure. When active plasma kallikrein had been produced, it activated inactive renin irreversibly. It appears unlikely that irreversible activation of inactive renin is taking place in the normal circulation where practically no active plasma kallikrein is present. (Hypertension 4: 102–111, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

To assess the effect of prostaglandin inhibition upon the vasoactive actions of endogenous and exogenous catecholamines in healthy man, indomethacin (150 mg/day for 3 days) was administered to six healthy men in the sodiumhyphenrepleted state. Pretreatment with indomethacin did not interfere with the response of blood pressure and pulse rate to orthostasis (10 minutes), a cold pressor test (2 minutes), and the intravenous (i.v.) administration of norepinephrine (NE) (50,100, and 200 ng kg1min1). Basal plasma concentrations of epinephrine (E) and NE as well as the concentrations of E during orthostasis and cold pressor test remained uninfluenced by pretreatment with indomethacin. While the release of NE during orthostasis appeared to be suppressed in the indomethacinhyphentreated state, it was unchanged during the cold pressor test. These results indicate that inhibition of endogenous prostaglandin synthesis may suppress the release of NE, but does not have a major impact on the vasoactive actions of endogenous and exogenous catecholamines in normal man. (Hypertension 4: 112–117, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

The effect of acute administration of captopril, an angiotensln converting enzyme inhibitor, on vascular responses of rings of rat aortic smooth muscle was tested in vitro. Dosehyphenresponse curres for various rasoactive agents were obtained before and after exposure to captopril (2 × 10−4M) for 30 minutes. In the presence of captopril, contractile responses to angiotensln I (5 × 10−10to 5 × 10−8M) were attenuated significantly, probably as a result of decreased local conversion of angiotensin I to angiotensin H. Contractile responses to angiotensin II (10−11to 5 × 10−0M) were not affected by captopril. All responses to norepinephrine (10−8to 10−4M) and phenyiephrine (10−8to 10−4M) were attenuated significantly from control in the presence of captopril. In the presence of the ahyphenadrenergic antagonist, phentolamine, captopril did not affect either the contractile responses to KG (30 to 100 mM) or the isoproterenolhypheninduced (10−8to 10−5M) relaxation of KGhyphendepolarized tissue. These results suggest that captopril decreased vascular responsiveness to α-adrenergic agonists but not to β-adrenergic agonists. Low concentrations of bradykinln (10−10to 10−4M) Induced contraction in KClhyphendepolarized tissue while higher concentrations (10−7and 10−4M) induced relaxation. In the presence of captopril, relaxation occurred at all concentrations of bradykinln (10−10to 10−4M), probably as a result of decreased degradation of the bradykinln. These data suggest depression of α-adrenergic responsiveness in vascular smooth muscle as another potential antihypertensive action of captopril. (Hypertension 4: 118–124, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

To investigate the relationship between sympathetic activity and blood flow in the kidney during propranolol treatment, 55 patients with uncomplicated essential hypertension were studied. Twentyhyphenfive of them had been treated with propranolol (average daily dose 240 mg) for about two weeks; the others served as untreated controls. In all patients renal arteriography was carried out, after which renal plasma flow (125I- hippuran clearance), cortical blood flow (xenonhyphenwashout), and renal release of noreplnephrine and renin were measured. In the propranolol group, renal plasma flow bad also been determined before treatment. Cardiac output (dyehyphendilution) and creatlnine clearance were measured both before as well as during therapy. In untreated hypertensives renal cortical blood flow was reduced to about 80% of what was predicted for the age level. On the basis of their changes in blood pressure, patients who were treated with propranolol were divided into responders (n = 15) and nonresponders (n = 10). Despite a similar fall in cardiac output in both subgroups, renal blood flow remained unchanged in responders, while it fell in nonresponders. In addition, renal norepinephrine release was significantly higher in nonresponders than in responders, while renin release in nonresponders was markedly suppressed. It may be concluded that sympathetic activity is an important determinant of renal (cortical) blood flow in essential hypertension. The effect of propranolol on the renal circulation depends, to some extent, on its unmasking of prevailing alphahyphenadrenergic tone. However, when blood pressure falls, an additional mechanism may be operative to cause renal vasodilation. (Hypertension 4: 125–131, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Several laboratories have reported evidence suggesting abnormalities in the activity of the sarcolemmal sodium pump in vascular smooth muscle in hypertension. Tbe present experiments were designed to investigate the relationship of such changes to the status of the renlnhyphenangiotensin-aldosterone system and body fluid volumes. We assessed sodium pump activity in vitro in sodiumhyphenloaded tail artery and thoracic aorta freshly excised from rats with chronic onehyphenkidney, one dip, and twohyphenkidney, one clip hypertension, and from appropriate normotensive control rats.$$Rb uptake in the absence (total uptake) and presence of 1.0 mM outbain (ouabalnhypheninsensitive uptake) was measured, and ouabainhyphensensitive uptake (nmole/mg dry weight/18 min) was calculated. Tbere were increases in plasma renin activity in the twohyphenkidney, one clip rats only. In the hypertensive rats tbere were significant increases (up to +60%) in tbe ouabainhyphensensitive and total$$Rb uptakes in both tail artery and aorta. Tbe magnitude of increases in arterial tissue uptakes in the two forms of Goldblatt hypertension, and in onehyphenkidney, one dip hypertensive rats given 0.9% saline to drink for 2 to 3 days before sacrifice, were similar. Further sodium loading of aortas from normotensive control rats did not increase their uptake. The results of this study provide no evidence for decreases in sodium pump activity, instead indicating that there are increases in the activity of the pump in the sarcolemma of arterial smooth muscle studied in vitro. These increases in pump activity do not appear to be related to altered activity of the reninangiotensin- aldosterone system, to changes in body fluid volumes, or to increases in intracellular concentrations of sodium. Increases in numbers or concentration of sarcolemmal pump molecules or in their turnover rate may be involved. However, in vitro MRb uptake by tail artery and aorta may not reflect the status of sodium pump activity in resistance vessels in vivo. (Hypertension 4: 132–139, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

Hypertensinogenic potency and other effects of acetate salts of aldosterone (ALA) and deoxycorticosterone (DOCA) were evaluated in 50-dayhyphenold mononephrectomized and salinehyphendrinking Sprague- Dawley CD male rats. The steroids were administered by continuous subcutaneous infusion in a dose of 100 μg/24 hrs by means of Alzet osmotic minipumps implanted subcutaneously. Within 3 weeks of steroid treatment, systolic Mood pressure, measured in the tail of conscious animals by a photoelectric cell method at 27°C environmental temperature, increased significantly in ALA rats as compared to that in DOCA rats, which was not different from controls. ALA rats exhibited marked polydipsia, decreased body weight, hypernatremia, hypokafemia, cardiomegaly, and kidney enlargement, whereas DOCA rats exhibited only cardiomegaly when compared with controls. The degree of cardiomegaly in ALA and DOCA rats was statistically much greater than the differences in their respective Mood pressure levels when compared to controls. Under the conditions of this study, it is concluded that: 1) the hypertensinogenic potency of ALA is greater than that of DOCA; 2) ALA and DOCA may induce cardiomegaly, independent of their effects on blood pressure; 3) Alzet osmotic minipumps are effective tools for the administration of steroids by continuous infusion. (Hypertension 4: 140–145, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID

摘要:

In six inbred dogs with neonatallyhypheninduced coarctation hypertension, and in seven littermate controls, acute responses of proximal arterial pressure and plasma renln activity (PRA) to converting enzyme inhibitor (CEI; SQ 20,881, 0.5 rag/kg i.v.) were serially examined. Studies were performed at 2, 6, and 12 months posthyphenaortic banding under sodiumhyphenreplete and -deplete conditions. Both in normotensive controls and in coarcted dogs, depressor responses (pre- minus posthyphenCEI values) were positively correlated, not only with initial (prehyphenCEI) PRA, but also independently with initial blood pressure. Although absolute depressor responses in coarcted dogs exceeded those of the control group, there were no significant group differences when, by analysis of covariance, depressor responses were adjusted for the physiologic influence of initial pressure. Similarly, depressor responses expressed as a percent of initial pressure were comparable in coarcted and control groups. Initial PRA and PRA response to CEI in coarcted dogs were also comparable to control dogs; the PRA response correlated with initial PRA in both groups. CEI did not significantly diminish the magnitude of bloodhyphenpressure difference between coarcted and control dogs. Thus, in neonatallyhypheninduced coarctation hypertension, under both sodium replete- and -deplete conditions: 1) acute depressor and PRA responses to CEI are modulated by the same factors that influence responses of normotensive controls; 2) larger absolute depressor responses to CEI appear to be a physiologic function of higher initial pressure; and 3) blood pressure excess over littermate controls is largely sustained by CEIhyphenresistant factors, potentially including the known volume excess in coarcted dogs. (Hypertension 4: 146–154, 1982)

ISSN:0194-911X    

出版商:OVID    

年代:1982

数据来源: OVID