Melaragno M G, Fink G D
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Am J Physiol. 1996 Aug;271(2 Pt 2):H806-11. doi: 10.1152/ajpheart.1996.271.2.H806.
These experiments tested the hypothesis that hypertension caused by chronic inhibition of nitiric oxide synthase (NOS) is associated with augmented pressor responsiveness to angiotensin II (ANG II). Antagonism of ANG II AT1 receptors with losartan caused a greater fall in blood pressure (BP) in rats treated for 2 wk with the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) than in normotensive rats. The delayed time course of the decline in BP implicated the slow pressor effect (SPE) of ANG II in L-NAME hypertension. Further experiments showed that direct elicitation of the SPE by continuous low-dose (4 ng/min) intravenous infusion of ANG II in enalapril-treated rats resulted in a larger chronic increase in BP if NOS was inhibited. However, L-NAME alone also caused a significant increase in BP in enalapril-treated rats. The combined effect on BP of ANG II and L-NAME was merely additive. These results confirm that ANG II is involved in L-NAME hypertension. However, chronic pressor responsiveness to the peptide is not augmented by L-NAME.
慢性抑制一氧化氮合酶（NOS）所导致的高血压与血管紧张素II（ANG II）的升压反应性增强有关。用氯沙坦拮抗ANG II的AT1受体，在接受NOS抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）治疗2周的大鼠中引起的血压（BP）下降幅度大于正常血压大鼠。血压下降的延迟时间进程表明ANG II的缓慢升压效应（SPE）参与了L-NAME高血压的形成。进一步的实验表明，在依那普利治疗的大鼠中，通过持续低剂量（4 ng/分钟）静脉输注ANG II直接引发SPE，如果NOS受到抑制，则会导致血压出现更大幅度的慢性升高。然而，单独使用L-NAME也会使依那普利治疗的大鼠血压显著升高。ANG II和L-NAME对血压的联合作用仅仅是相加性的。这些结果证实ANG II参与了L-NAME高血压的形成。然而，L-NAME并未增强对该肽的慢性升压反应性。
