ANGIOTENSIN-(1-7) AND NITRIC-OXIDE INTERACTION IN RENOVASCULAR HYPERTENSION
ANGIOTENSIN-(1-7) AND NITRIC-OXIDE INTERACTION IN RENOVASCULAR HYPERTENSION
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DOI：
10.1161/01.hyp.25.4.796
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发表时间：
1995-04-01
期刊：
影响因子：
8.3
通讯作者：
DEAN, RH
中科院分区：
文献类型：
--
作者：
NAKAMOTO, H;FERRARIO, CM;DEAN, RH
新的研究表明，血管扩张系统可能在抑制与动脉高血压进展相关的外周血管阻力升高方面发挥重要作用。我们的特点是在清醒的狗的血液动力学和激素的影响，4周的喂养一氧化氮合酶抑制剂N-ω-硝基-L-精氨酸（3毫克。kg-（1）。d（-1））或一氧化氮前体L-精氨酸（0.3 mg . k（-1）。d（-1））两肾一夹型高血压演变过程中。抑制一氧化氮的产生引起的高血压比安慰剂喂养的两肾一夹犬更严重。血压水平越高。伴随着较低水平的血浆肾素活性和较低的血管紧张素II浓度。在肾血管性高血压的慢性阶段，在给予一氧化氮抑制剂的狗中，由急性全身注射赖诺普利或氯沙坦引起的血压下降显著减少。相反，长期服用L-精氨酸对高血压的程度或与肾性高血压演变相关的肾素活性和高血管紧张素血症的增加没有影响。同样，药物阻断血管紧张素II引起的血压下降与未治疗的肾性高血压犬的血压下降没有差异。静脉注射血管紧张素-（1-7）（1 - 100 nmol/kg）引起的血压反应的血管舒张成分在未治疗和L-精氨酸治疗的两肾一夹高血压犬中均增加，但在喂食一氧化氮合酶抑制剂的高血压犬中显著减弱。这些实验表明，在肾血管性高血压的发展过程中，一氧化氮在调节外周肾素-血管紧张素系统活性增加方面有重要作用。此外，我们的数据表明，这种形式的实验性肾性高血压的演变伴随着血管紧张素-（1-7）的血管扩张作用的放大。内皮源性舒张因子和血管紧张素-（1-7）机制的激活可能协同作用，以缓冲慢性肾缺血引起的血管阻力增加。
New studies suggest that vasodilator systems may play an important role in restraining the rise in peripheral vascular resistance associated with the evolution of arterial hypertension. We characterized in conscious dogs the hemodynamic and hormonal effects of 4 weeks of feeding either the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (3 mg . kg-(1) . d(-1)) or the nitric oxide precursor L-arginine (0.3 mg . k(-1) . d(-1)) during the evolution of two-kidney, one clip hypertension. Inhibition of nitric oxide production elicited a form of hypertension more severe than that produced in placebo-fed two-kidney, one clip dogs. The higher levels of blood pressure were. accompanied by lower levels of plasma renin activity and lower angiotensin II concentrations. During the chronic phase of renovascular hypertension, the fall in blood pressure produced by acute systemic injections of lisinopril or losartan was significantly reduced in dogs given the nitric oxide inhibitor. In contrast, chronic administration of L-arginine had no effect on the magnitude of hypertension or on the increases in renin activity and hyperangiotensinemia associated with the evolution of renal hypertension. Likewise, the fall in blood pressure produced by pharmacological blockade of angiotensin II was not different from that recorded in untreated renal hypertensive dogs. The vasodilator component of the blood pressure response due to intravenous injections of angiotensin-(1-7) (1 to 100 nmol/kg) was augmented in both untreated and L-arginine-treated two-kidney, one clip hypertensive dogs, but was significantly attenuated in hypertensive dogs fed the nitric oxide synthase inhibitor. These experiments demonstrated an important contribution of nitric oxide in modulating the increased activity of the peripheral renin-angiotensin system during the evolution of renovascular hypertension. Furthermore, our data show that the evolution of this form of experimental renal hypertension is accompanied by a magnification of the vasodilator actions of angiotensin-(1-7). Activation of endothelium-derived relaxing factors and angiotensin-(1-7) mechanisms may act in synergy to buffer the increase in vascular resistance produced by chronic renal ischemia.