Intrarenal vascular effects of [des-Asp1] angiotensin I and angiotensin III in the dog.

Abstract

SUMMARY We determined the effects of direct renal intra-arterial injections of [des-Asp^angiotensin I (0.2-3.2 pg) and angiotensin HI (0.00625-0.1 fig) on renal blood flow in 10 dogs anesthetized with pentobarbitaL Both [des-Asp*]angiotensin I and angiotensin HI caused dose-dependent decreases in renal blood flow. The decreases in ipsilateral renal blood flow occurred in the absence of alterations in systemic arterial pressure and flow to the contralateral kidney, suggesting that the response was a local event. The renovascular responses to [des-Asp'jangiotensin I were greatly attenuated during the intravenous administration of SQ 20881, a synthetic peptide that competitively inhibits angiotensin converting enzyme., SQ 20881 did not alter the vasoconstrictor responses to angiotensin EH, angiotensin n, or norepinephrine. [Ue'jAngiotenain HI (an angiotensin HI antagonist) abolished decreases in renal blood flow produced by [des-Asp'langiotenflin L, angiotensin H angiotensin HL and angiotensin I, whereas the response to norepinephrine was unchanged. These results suggest that the decrease in renal blood flow produced by [des-Asp'Jangiotensin I is due to its local enzymatic conversion to angiotensin HI. About 7% of [des-Asp'Jangiotensin I is converted to angiotensin HI during one transit through the kidney. Circ Res 44:666-671, 1979 IT HAS BEEN demonstrated recently that [desAsp'jangiotensin LI (angiotensin III) is as potent as angiotensin II in decreasing renal blood flow, and it was hypothesized that the local production of angiotensin HI occurs at the level of the renal arteriolar receptor (Freeman et aL, 1975). Data are available to support the existence of two pathways for the generation of angiotensin HI: the first from angiotensin II by the cleavage of the N-terminal aspartic acid through the action of aminopeptidases (Glenner et al., 1962; Regoli et al., 1963), and the