Effects of paired analogs of angiotensin II and angiotensin III on rat smooth muscle.

The effects of several paired analogs of angiotensin II and angiotensin III, designed as antagonists, have been compared in isolated smooth muscle (rat uterus) and by in vivo rat blood pressure assay. These analogs were (1) the angiotensin II series: (1-sarcosine, 7-X, 8-isoleucine-) angiotensin II, and (2) the angiotensin III series: (1-despartyl, 7-X, 8-isoleucine)angiotensin II, where X=sarcosine, N-methyl-L-alanine or DL-nipecotic acid. All of these analogs had very low pressor and myotropic activities in the vagotomized, ganglion-blocked rat and the isolated rat uterus, respectively, although the angiotensin II analogs had significantly higher intrinsic pressor activity than the angiotensin III analogs. In addition, the angiotensin II analogs were potent antagonists of the contractile response to angiotensin II in the rat uterus whereas the angiotensin III analogs were weak inhibitors. These observations demonstrate the existence of functional differences for the proline residue in angiotensin II and angiotensin III analogs and may reflect differences in conformation and modes of binding to smooth muscle receptors between the two classes of peptides.