Angiotensin I, II, and II tachyphylaxis in the mesenteric vascular circuit of the rat

Angiotensin tachyphylaxis is rapidly induced in the mesenteric vascular circuit of the rat perfused with a saline solution. there is crossed tachyphylaxis among angiotensins (AI, AII, and AIII). The angiotensin antagonist Sar 1-Ileu 8-AII is ineffective when the vascular preparation is previously rendered tachyphylactic to AII, showing that the AII receptors are not available during tachyphylaxis. This finding supports the theory that angiotensin tachyphylaxis is caused by receptor occupancy by the agonist. By perfusing the vascular preparation with aII solutions that were too diluted to produce vasoconstriction, tachyphylaxis to AII was induced. Therefore, AII receptors can be slowly saturated without producing vasoconstriction. The recoveries of the vasoconstrictor effect of AII and AIII at 30 and 60 minutes after tachyphylaxis are similar; thus, the dissociation constants of the AII- and AIII-receptor complexes should be alike. After three bolus injections of AI, the vascular preparation is completely refractory to AI, AII, and AIII. When the conversion of AI to AII is inhibited with captopril, AI no longer induces tachyphylaxis to AII and AIII. Thus, tachyphylaxis to AII and AIII induced by AI seems to be due not to the occupancy of AII receptors by AI but to the AII formation from AI "in situ."