Madwed J B, Winquist R J
Department of Pharmacology, Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877.
J Hypertens. 1994 Feb;12(2):159-62.
We have found that low-dose infusion of angiotensin II (Ang II) selectively potentiates the mean arterial pressure (MAP) response to phenylephrine in pentobarbital-anesthetized rabbits.
To examine whether endogenous Ang II levels in normotensive rabbits maintained on a normal-salt diet exert a potentiating effect on the MAP response to phenylephrine.
We compared the effects of enalaprilat (0.3 mg/kg per min for 5 min bolus, 1 mg/kg per h infusion), losartan (DuP753; 4 mg/kg bolus, 2 mg/kg per h infusion) and vehicle administration on the MAP response to infusions of phenylephrine that were increased incrementally (2.5, 5 and 10 micrograms/kg per min).
Enalaprilat decreased MAP significantly, whereas no maintained change was observed with losartan or vehicle. Phenylephrine infusions elevated MAP significantly and dose-dependently in all of the rabbits studied, but this effect was attenuated significantly in the rabbits given losartan compared with in those given vehicle or enalaprilat. The heart rate responses were not significantly different among the three groups.
We conclude that inhibition of the renin-angiotensin system at two distinct sites results in different MAP responses to phenylephrine infusion.
我们发现，在戊巴比妥麻醉的兔中，低剂量输注血管紧张素II（Ang II）可选择性增强去氧肾上腺素引起的平均动脉压（MAP）反应。
研究正常盐饮食的正常血压兔体内内源性Ang II水平是否对去氧肾上腺素引起的MAP反应具有增强作用。
我们比较了依那普利拉（0.3 mg/kg每分钟推注5分钟，1 mg/kg每小时输注）、氯沙坦（DuP753；4 mg/kg推注，2 mg/kg每小时输注）和给予赋形剂对递增输注去氧肾上腺素（2.5、5和10微克/千克每分钟）引起的MAP反应的影响。
依那普利拉显著降低MAP，而氯沙坦未观察到持续变化。在所有研究的兔中，输注去氧肾上腺素均显著且剂量依赖性地升高MAP，但与给予赋形剂或依那普利拉的兔相比，给予氯沙坦的兔中这种作用显著减弱。三组之间的心率反应无显著差异。
我们得出结论，在两个不同位点抑制肾素-血管紧张素系统会导致对输注去氧肾上腺素产生不同的MAP反应。
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