Mitchell K D, Navar L G
Department of Physiology, Tulane University School of Medicine, New Orleans, La.
Ren Physiol Biochem. 1991 Jul-Oct;14(4-5):155-63. doi: 10.1159/000173401.
There is growing recognition that angiotensin II (ANG II) formed intrarenally exerts direct effects on renal hemodynamics and tubular reabsorption. In vivo micropuncture experiments performed in anesthetized rats have shown that peritubular capillary infusion of either ANG II or angiotensin I (ANG I), at rates that do not markedly influence baseline vascular resistance, can increase proximal tubular reabsorption rate and enhance the responsiveness of the tubuloglomerular feedback mechanism. With higher ANG II or ANG I infusion rates, pronounced preglomerular vasoconstriction occurs, resulting in reduced glomerular capillary pressure and single nephron glomerular filtration rate. The effects of peritubular capillary infusion of ANG I on glomerular function have been shown to be inhibited by the ANG II receptor antagonist, saralasin, indicating that the observed effects of ANG I on proximal tubular reabsorption and glomerular function are not due to direct effects of the decapeptide but are mediated by increases in the interstitial ANG II concentrations resulting from intrarenally generated ANG II. Interestingly, neither peritubular capillary infusion nor systemic administration of large doses of the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat, elicited significant blockade of the single nephron hemodynamic responses to peritubular infusion of ANG I. These findings indicate that intrarenal conversion of ANG I to ANG II occurs, at least in part, at a site which is inaccessible to acutely administered ACE inhibitors, or that there is an alternative pathway for the intrarenal conversion of ANG I to ANG II that is not blocked by ACE inhibitors.
越来越多的人认识到，肾内生成的血管紧张素II（ANG II）对肾血流动力学和肾小管重吸收有直接影响。在麻醉大鼠身上进行的体内微穿刺实验表明，以不会显著影响基线血管阻力的速率向肾小管周围毛细血管输注ANG II或血管紧张素I（ANG I），可增加近端肾小管重吸收率并增强肾小管-肾小球反馈机制的反应性。当ANG II或ANG I输注速率更高时，会出现明显的肾前血管收缩，导致肾小球毛细血管压力和单肾单位肾小球滤过率降低。已证明，ANG II受体拮抗剂沙拉新可抑制向肾小管周围毛细血管输注ANG I对肾小球功能的影响，这表明观察到的ANG I对近端肾小管重吸收和肾小球功能的影响并非源于十肽的直接作用，而是由肾内生成的ANG II导致的间质ANG II浓度升高介导的。有趣的是，无论是向肾小管周围毛细血管输注还是全身给予大剂量的血管紧张素转换酶（ACE）抑制剂依那普利拉，都未对单肾单位对肾小管周围输注ANG I的血流动力学反应产生显著阻断作用。这些发现表明，ANG I在肾内转化为ANG II至少部分发生在急性给予的ACE抑制剂无法到达的部位，或者存在ANG I在肾内转化为ANG II的替代途径，而该途径不会被ACE抑制剂阻断。
