Petide antagonists of the renin-angiotensin system in the characterisation of receptors for angiotensin-induced drinking

Abstract

The two naturally occurring analogues of angiotensin II (AII), Asp1-Val5-AII and Asp1-Ile5-AII, were equally effective as intracranial dipsogens in the water-replete rat. Renin, synthetic tetradecapeptide renin substrate (SRS) and angiotensin I (AI) also produced copious drinking when injected into the brain, but the naturally occurring renin substrate of rat caused little drinking and was much less effective than SRS. Prior intracranial injection of pepstatin, a competitive antagonist of the renin-angiotensinogen reaction, reduced drinking in response to renin and SRS but not to AI and AII. Renin-, SRS- and AI-induced drinking were inhibited by the converting enzyme inhibitor SQ 20881 injected through the same intracranial cannula in antagonist to agonist ratio of 1000:1, whereas the AII response was enhanced, although not significantly so, and the carbachol response was unaffected. Finally, position 8 aliphatic substituted analogues of AII were competitive antagonists of AII-induced drinking, and also inhibited drinking induced by renin, SRS and AI injected through the same intracranial cannula, but they did not inhibit carbachol-induced drinking. In conclusion, the angiotensin-sensitive receptor for thirst does not accept SRS or AI. It responds best to AII.