Novel selective hypotensive vasopressin peptides: cardiovascular and structure-activity-relationship studies

Recently, we discovered a series of peripheral acting selective hypotensive vasopressin peptides. Whether these peptides may interact with receptors outside the vasopressin receptor family and affect cardiac function could not be excluded. Accordingly, we tested the effects of these hypotensive vasopressin peptides on blood pressure and heart rate in intact rats and on the heart rate, ventricular contractile force and coronary flow of isolated perfused rat hearts. We found that the hypotensive vasopressin peptides did not modify cardiac function, either in vivo or in vitro. The vasodepressor potency was reduced when assayed in rats with vasopressin-maintained baseline blood pressure, suggesting that vasopressin and the hypotensive peptide compete for a common vasodilating vasopressin receptor in the vasculature. We have now synthesized more potent and radioiodinatable hypotensive peptides that could serve as lead compounds for the development of a radiomarker for the putative vasodilating vasopressin receptor.