Renal vascular tachyphylaxis to angiotensin II: specificity of the response for angiotensin

Hypotheses concerning angiotensin's role in states characterized by severe and sustained renal vasoconstriction, must account for the poorly sustained renal response to this agent in healthy animals and man. To assess the specificity of renal vascular tachyphylaxis to angiotensin II (AII), renal blood flow was measured with an electromagnetic flowmeter in eight anesthetized dogs. Bolus injections of AII and norepinephrine into the renal artery were adjusted to produce at least a 50% reduction in renal blood flow, and were followed by a continuous infusion of AII sufficient to reduce renal blood flow acutely by 60 +/- 10%. The response to the continuous infusion was poorly sustained, blood flow returning to near baseline within 10 minutes: At this time the response to bolus administration of AII was lost, but the response to norepinephrine was sustained. At 30 minutes the response to norepinephrine was also reduced, and there was no response in three of the eight dogs. After stopping the AII infusion, renal vascular responsiveness to norepinephrine returned almost immediately, but 30-60 minutes were required before responsiveness to AII was restored. We conclude that there is true, specific renal vascular tachyphylaxis to AII--which may well reflect receptor modulation or occupation--and that with time an additional, non-specific vasodilator mechanism can come into play.