Abstract

Angiotensin II (AII) receptors in guinea pig isolated esophageal muscularis mucosae (EMM), stomach fundus, gall bladder, ileum, colon and thoracic aorta have been characterized by peptide agonists and nonpeptide antagonists in the presence of peptidase inhibitors. Angiotensin peptides contracted every preparation studied; the potency order typically was [Sar1]AII > or = AII > angiotensin III (AIII) > or = [Val4]AIII > AI > [des Phe8]AII. AI was ineffective everywhere except the gall bladder, where it acted as a full agonist. Tetrodotoxin (1 microM) and atropine (1 microM) did not affect the AII response in EMM, fundus and gall bladder. In ileum, AII and AIII were equieffective, and both the maximal response and potency were decreased by tetrodotoxin and atropine. Indomethacin (3 microM) abolished response to AII in the fundus but had little effect on the gall bladder and the atropine-resistant component of the ileal response. The AT1-selective antagonist losartan (DuP 753) antagonized responses to AII in all tissues with similar affinities when there was no depression of maximal response (pKB = approximately 8-8.3). The AT2-selective antagonist PD123177 (10 microM) failed to antagonize responses to AII in any tissue. These data suggest the presence of AT1 receptors in intestinal and vascular smooth muscles of the guinea pig. It is unclear whether all AT1 receptors are similar because of the differential potency order observed in the presence of peptidase inhibitors. Of the isolated tissue investigated, responses to AII are robust and reproducible in the ileum, fundus and gall bladder.