Berthold H, Münter K, Just A, Kirchheim H R, Ehmke H
I. Physiologisches Institut der Ruprecht-Karls-Universität Heidelberg, 69120 Heidelberg, Germany.
Am J Physiol. 1999 Mar;276(3):F417-24. doi: 10.1152/ajprenal.1999.276.3.F417.
Exogenous endothelin-1 (ET-1) is a strong vasoconstrictor in the canine kidney and causes a decrease in renal blood flow (RBF) by stimulating the ETA receptor subtype. The aim of the present study was to investigate the role of endogenously generated ET-1 in renal hemodynamics under physiological conditions. In six conscious foxhounds, the time course of the effects of the selective ETA receptor antagonist LU-135252 (10 mg/kg iv) on mean arterial blood pressure (MAP), heart rate (HR), RBF, and glomerular filtration rate (GFR), as well as its effects on renal autoregulation, were examined. LU-135252 increased RBF by 20% (from 270 +/- 21 to 323 +/- 41 ml/min, P < 0.05) and HR from 76 +/- 5 to 97 +/- 8 beats/min (P < 0. 05), but did not alter MAP, GFR, or autoregulation of RBF and GFR. Since a number of interactions between ET-1 and the renin-angiotensin system have been reported previously, experiments were repeated during angiotensin converting enzyme (ACE) inhibition by trandolaprilat (2 mg/kg iv). When ETA receptor blockade was combined with ACE inhibition, which by itself had no effects on renal hemodynamics, marked changes were observed: MAP decreased from 91 +/- 4 to 80 +/- 5 mmHg (P < 0.05), HR increased from 85 +/- 5 to 102 +/- 11 beats/min (P < 0.05), and RBF increased from 278 +/- 23 to 412 +/- 45 ml/min (P < 0.05). Despite a pronounced decrease in renal vascular resistance over the entire pressure range investigated (40-100 mmHg), the capacity of the kidneys to autoregulate RBF was not impaired. The GFR remained completely unaffected at all pressure levels. These results demonstrate that endogenously generated ET-1 contributes significantly to renal vascular tone but does not interfere with the mechanisms of renal autoregulation. If ETA receptors are blocked, then the vasoconstrictor effects of ET-1 in the kidney are compensated for to a large extent by an augmented influence of ANG II. Thus ET-1 and ANG II appear to constitute a major interrelated vasoconstrictor system in the control of RBF.
外源性内皮素 -1（ET -1）是犬肾中的一种强效血管收缩剂，通过刺激ETA受体亚型导致肾血流量（RBF）减少。本研究的目的是探讨内源性生成的ET -1在生理条件下对肾血流动力学的作用。在6只清醒的猎狐犬中，研究了选择性ETA受体拮抗剂LU -135252（10 mg/kg静脉注射）对平均动脉血压（MAP）、心率（HR）、RBF和肾小球滤过率（GFR）的影响的时间进程，以及其对肾自身调节的影响。LU -135252使RBF增加了20%（从270±21增加到323±41 ml/min，P < 0.05），HR从76±5增加到97±8次/分钟（P < 0.05），但未改变MAP、GFR或RBF和GFR的自身调节。由于先前已报道ET -1与肾素 - 血管紧张素系统之间存在多种相互作用，因此在使用trandolaprilat（2 mg/kg静脉注射）抑制血管紧张素转换酶（ACE）期间重复了实验。当ETA受体阻断与ACE抑制联合使用时（ACE抑制本身对肾血流动力学无影响），观察到明显变化：MAP从91±4降至80±5 mmHg（P < 0.05），HR从85±5增加到102±11次/分钟（P < 0.05），RBF从278±23增加到412±45 ml/min（P < 0.05）。尽管在所研究的整个压力范围（40 - 100 mmHg）内肾血管阻力显著降低，但肾脏自身调节RBF的能力并未受损。在所有压力水平下，GFR均完全不受影响。这些结果表明，内源性生成的ET -1对肾血管张力有显著贡献，但不干扰肾自身调节机制。如果ETA受体被阻断，那么ET -1在肾脏中的血管收缩作用在很大程度上会被ANG II增强的影响所补偿。因此，ET -1和ANG II似乎构成了控制RBF的主要相互关联的血管收缩系统。
