Renal hemodynamic and tubular effects of angiotensins II and III

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(+)-H+ exchange. A stimulatory effects of ANG II at low dose (10(-12)-10(-9) M) and an inhibitory effect at higher dose (10(-7)-10(-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 Ile7-ANG III and potentiated by bestatin, suggesting that the heptapeptide may also play an active role in the regulation of sodium excretion by actions on renal hemodynamics and tubules.