Abstract

These experiments were undertaken to determine the comparative relationships between chemical structure and biologic (contractile) activity of a series of vasopressin hormone analogs on different rat blood vessels (e.g., aorta, mesenteric arteriole and mesenteric venule). The functional contributions to, and interactions with, phenolic hydroxyl and aromatic groups as well as basicity in positions 2, 3 and 8, respectively, to or with hormone-receptor affinity and intrinsic (contractile) activity, were determined by analyzing the dose-response curves of five vasopressin peptides lacking one or more of these functional groups. The findings demonstrate that: 1) the structure-action relationships for vasopressin peptide-induced contractions on rat blood vessels vary with the particular type of macro- or microvessel (i.e., aorta, arteriole and venule); 2) the phenolic and aromatic groups in positions 2 and 3, respectively, are not only important for hormone-receptor affinity but intrinsic activity as well; 3) the potency (EC50) values for arginine vasopressin as well as the potencies and intrinsic activities of synthetic vasopressin analogs varied between the three different types of rat blood vessels examined; and 4) circulating levels (i.e., 10- minus 11- minus 10- minus 12 M) of [8-arginine]-vasopressin are capable of inducing contractile effects on mesenteric arterioles and venules. The quantitative data obtained in this study support the notion that a heterogeneity of the receptor, which subserves contraction, probably exists in blood vessels within and between vascular beds of a single mammalian species.