Renal Hemodynamic and Tubular Effects of AngiotensinsⅡand Ⅲ

Huang, W.C. Renal hemodynamic and tubular effects of angiotensins Ⅱ andⅢ. Chinese J. Physiol. 34(1): 121-138, 1991. Angiotensin Ⅱ (ANG Ⅱ) plays an important role in the regulation of renal vascular resistance, glomerular function and tubular reabsorption. Systemic infusion of ANG Ⅱ produces dose-dependent decreases in renal blood flow (RBF), glomerular filtration rate (GFR) and filtration coefficient, and increases in filtration fraction. Intrarenally generated ANG Ⅱ is also critical to alterations in cortical and juxtamedullary glomerular ultrafiltration. On the other hand, pharmacological blockade of the systemical and intrarenal generation or action of ANG Ⅱ elicits increases in RBF and pressure-associated changes in GFR In vivo micropuncture experiments demonstrate that peritubular capillary microperfusion of 10^(-7) M ANG Ⅱ results in decreases in single nephron GFR and glomerular capillary pressure. Blockade of ANG Ⅱ activity by ANG converting enzyme (ACE) inhibitor markedly attenuates, whereas intravenous or peritubular capillary infusion of exogenous ANG Ⅱ enhances tubuloglomerular feedback (TGF) mediated changes in the stop flow pressure. Moreover, infusion of exogenous ANG Ⅱ during conditions of ACE blockade partially restores the feedback responsiveness, suggesting a specific role of ANG Ⅱ as a modulator of TGF system. Besides its effects on intrarenal hemodynamics, ANG Ⅱ directly or indirectly affects renal sodium excretion. Micropuncture and microperfusion studies have shown that ANG Ⅱ exerts a dose-dependent biphasic effect on proximal tubular sodium reabsorption via apical Na(superscript +)-H(superscript +) exchange. A stimulatory effects of ANG Ⅱ at low dose (10^(-12)-10^(-9)M) and an inhibitory effect at higher dose (10^(-7)-l0^(-5)M) have been observed in the cortical and juxtamedullary nephron preparations. The stimulatory effect of ANG Ⅱ on proximal tubular reabsorption of sodium seems associated with reduction in cAMP and/or activation of protein kinase C, whereas cytosolic free calcium surge activated by ANG Ⅱ may be part of the cellular message that inhibits proximal tubular reabsorptive function. ANG Ⅲ, a metabolite of ANG Ⅱ, also enters substantial influence on renal function. In contrast to the systemic pressor effect, the two peptides are approximately equipotent in their actions on the renal vasculature. Superimposed administration of either ANG Ⅱ or ANG Ⅲ during ACE inhibition completely reverses the GFR and renal excretory responses to ACE inhibition. Furthermore, intracerebroventricular injections of ANG Ⅱ and ANG Ⅲ in rats inhibit renal nerve activity and cause a comparable renal effect which can be blocked by Ile^7-ANG Ⅲ and potentiated by bestatin, suggesting that the heptapeptide tide may also play an active role in the regulation of sodium excretion by actions on renal hemodynamics and tubules.

並列關鍵字

angiotensinⅡ ； angiotensin Ⅲ ； angiotensin converting enzyme inhibitor ； tubuloglomerular feedback ； GFR ； natriuresis ； diuresis ； renal nerve

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