Inhibitory Effects of LY301875 on Responses to Angiotensin Peptides in Pulmonary Vascular Bed of the Cat.

Abstract

The effects of the nonpeptide angiotensin receptor antagonist LY301875 on responses to angiotensin II, angiotensin III, and angiotensin IV were investigated in the pulmonary vascular bed of the intact cat chest. Under conditions of controlled blood flow, injections of the angiotensin peptides into the perfused lobar artery caused dose-related increases in lobar arterial pressure, and LY301875 decreased pressor responses to angiotensin II, angiotensin III, and angiotensin IV. The duration of the blockade was related to the dose of the antagonist, and LY301875 had no significant effect on pressor responses to U-46619, norepinephrine, serotonin or BAY K 8644. LY301875 caused minimal decreases on mean baseline systemic arterial pressures and did not significantly affect lobar arterial pressure in the cat. These results indicate that LY301875 is a potent selective long-acting angiotensin receptor antagonist and suggest that this agent may be useful in the investigation of the role of angiotensin peptides in physiological and pathophysiological processes in the pulmonary vascular bed.