The role of endogenous bradykinin in blood pressure homeostasis in spontaneously hypertensive rats

被引:10
作者
Holte, HR [1 ]
BjornstadOstensen, A [1 ]
Berg, T [1 ]
机构
[1] UNIV OSLO,INST BASIC MED SCI,DEPT PHYSIOL,OSLO,NORWAY
关键词
bradykinin; bradykinin antagonist; converting enzyme inhibitor; captopril; NO; sympathetic nervous system; blood pressure; hypertension;
D O I
10.1111/j.1476-5381.1996.tb15626.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The role of endogenous bradykinin in mean arterial blood pressure (BP) homeostasis was studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats by the use of a bradykinin B-2-receptor antagonist (BKant; Hoe 140, 11.6 mu g kg(-1)) and converting enzyme (kininase II) inhibitor (captopril, 10 mg). To obtain a response to captopril that was induced through inhibition of kinin-degradation only and not through inhibition of angiotensin II-formation, the studies were performed on binephrectomized male rats to eliminate the renin-angiotensin system. 2 The role of the nitric oxide (NO) and the adrenergic systems were evaluated by the use of NO-synthase inhibitor (L-NAME, 0.3 g kg(-1)) and phentolamine (2 mg kg(-1)), respectively. 3 The rats were anaesthetized and pretreated with two injections of vehicle (PBS) or drugs spaced 5 min apart: PBS + PBS; BKant + PBS; PBS + L-NAME; BKant + L-NAME; or phentolamine + L-NAME. All rats were given captopril 15 min later. Time-control groups were treated with L-NAME but not captopril. 4 In WKY rats, captopril did not significantly alter BP in any of the groups. In the SHR-PBS + PBS group, on the other hand, captopril induced an immediate fall in BP (Delta BP = -23 +/- 4 mmHg, P<0.0017) which was completely blocked by BKant (Delta BP = 2 +/- 2 mmHg) (P<0.0011). L-NAME did not significantly alter the immediate hypotensive response to captopril but disclosed a later hypertensive reaction. In L-NAME + BKant-treated rats, both the hypotensive response and the late hypertension was abolished. In rats treated with phentolamine + L-NAME, the immediate fall in BP was not different from the controls whereas the late hypertension was absent. 5 BKant itself had no effect on basal BP in either WKY or SHR even when a 10 times higher dose was tested in a separate set of experiments. This was true also for conscious, nonnephrectomized SHR rats. 6 It was concluded that endogenous production of bradykinin was demonstrable through kininase II-inhibition in hypertensive but not in normotensive rats. However, this endogenous bradykinin did not play a role in basal BP homeostasis. The captopril-induced hypotension depended on kinin but, under the present conditions, not on NO as a mediator. The fall in BP induced a compensatory adrenergic hypertensive response which was revealed when the continuous NO-synthesis was blocked by L-NAME.
引用
收藏
页码:1925 / 1930
页数:6
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