SOME ASPECTS OF THE PHARMACOLOGY OF VALYL⁵--(PYRAZOLYL-3)-L-ALANYL⁶-ANGIOTENSIN II

¹ Department of Pharmacology, School of Pharmacy, and the Protein Research Laboratory, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania

Several pharmacologic actions of valyl⁶--(pynazolyl-3)-L-alanyl⁶-angiotensin II (Val⁵-Pyr(3) Ala⁶-angiotensin II) were investigated and compared to those produced by Val⁵-angiotensin II. The Pyr(3) Ala⁶ derivative possessed 53.4% of the pressor activity of Val⁵-angiotensin II in the pithed rat and 52.9 to 55.7% in the anesthetized dog. The Pyr(3) Ala⁶ analog caused an increase in the tension developed by the isolated guinea-pig ileum preparation. Log dose-response curves were linear and parallel, and the analog possessed 23.8% of the intestinal stimulating activity of Va1⁵angiotensin II. The peptide was capable of producing a centrally mediated pressor response which was 48% that of Val⁵-angiotensin II. Val⁵-Pyr(3) Ala⁶-angiotensin II also produced an elevation of the aldostenone output from the adrenal glands of dogs which was less than that produced by Val⁵-angiotensin II. The results of this investigation suggest that, although the degree of ionization of the imidazole ring may not be a requirement for biologic activity, this ring structure may be necessary for activation of receptors.