Interaction between nitric oxide and endogenous vasoconstrictors in control of renal blood flow
Interaction between nitric oxide and endogenous vasoconstrictors in control of renal blood flow
复制标题
DOI：
10.1161/01.hyp.34.6.1254
复制
发表时间：
1999-12-01
期刊：
影响因子：
8.3
通讯作者：
Ehmke, H
中科院分区：
文献类型：
--
作者：
Berthold, H;Just, A;Ehmke, H
肾血流量(RBF)水平由相反的血管收缩和血管扩张影响控制。在最近的一项对正常血压狗的研究中，我们发现联合阻断内皮素A型(ETA)受体和血管紧张素II的形成可以显著增加RBF，这比单独阻断任何一个系统的影响都要大得多。本研究的目的是确定一氧化氮(NO)在这种血管扩张反应中的作用。实验在6只清醒的、长期固定的狗身上进行，分别在不同的日子里接受5种不同的实验处理。与时间控制实验相比，选择性拮抗剂鲁135252单独阻断ETa受体对RBF的影响较小。另外，用血管紧张素转换酶抑制剂曲度拉普利拉阻断血管紧张素II的形成，可使RBF显著增加约50%。当用N-G-硝基-L-精氨酸甲酯盐酸盐抑制NO合成酶时，这种血管扩张完全被抑制。然而，在NO合成酶抑制期间，通过输注NO供体S-亚硝基-N-乙酰基-D，L-青霉胺将肾血管NO浓度钳制在对照水平时，血管扩张反应完全恢复(Delta RBF接近60%)。这些结果表明，ETA受体阻断和血管紧张素转换酶抑制联合应用后的血管扩张不是通过增加NO的释放来实现的，而是由正常情况下由结构性释放的NO所产生的紧张性影响被掩盖的结果。因此，内皮型一氧化氮合酶的紧张性活性在肾血管阻力的生理调节中具有重要作用，因为它决定了血管舒缩反应对内皮素和血管紧张素II的反应。
The level of renal blood flow (RBF) is controlled by opposing vasoconstrictor and vasodilator influences. In a recent investigation in normotensive dogs, we found that combined blockade of endothelin type A (ETA) receptors and angiotensin II. formation induces marked increases in RBF that were much larger than the effects of blocking either system alone. The aim of the present study was to determine the contribution of nitric oxide (NO) to this vasodilator response. Experiments were made in 6 conscious, chronically instrumented dogs subjected to 5 different experimental treatments on separate days. Blockade of ETA receptors alone by the selective antagonist LU 135252 had only minor effects on RBF compared with time-control experiments. Additional blockade of angiotensin II formation by angiotensin-converting enzyme inhibition with trandolaprilat caused a substantial increase of RBF by approximate to 50%. This vasodilation was entirely suppressed when NO formation was prevented by inhibition of NO synthase with N-G-nitro-L-arginine methyl eater HCl. However, when during NO synthase inhibition renal vascular NO concentrations were clamped at control levels by infusing the NO donor S-nitroso-N-acetyl-D,L-penicillamine, the vasodilator response to combined blockade of ETA receptors and angiotensin II formation was completely restored (Delta RBF approximate to 60%). These results indicate that the vasodilation after combined ETA receptor blockade and angiotensin-converting enzyme inhibition is not mediated by an increase in NO release but results from the unmasking of the tonic influence that is normally exerted by constitutively released NO. Accordingly, the tonic activity of endothelial NO synthase appears to be of major importance in the physiological regulation of renal vascular resistance by determining the vasomotor responses to endothelin and angiotensin II.