RESPONSES TO A NONPEPTIDE ANGIOTENSIN RECEPTOR AGONIST, L-163491, IN THE FELINE PULMONARY VASCULAR BED

The mechanism by which a novel potent non-peptide angiotensin subtype 1 receptor (AT(1)) agonist, (5,7-dimethyl-2-ethyl-3-[[2'-[(butyloxycar bonyl) lfonyl]-5'-(3-methoxybenzyl)-[1,1'-biphenyl]-4-yl] methyl]-3H-i midazo [4,5-b] pyridine) (L-163,491), increased pulmonary vascular res istance was investigated in the intact-chest anesthetized cat under co nditions of controlled blood flow. Intralobar injections of L-163,491, in doses of 10-300 mu g i.a., caused dose-related increases in lobar arterial pressure that were partially antagonized by an AT(1) receptor antagonist, DuP 532, or by staurosporine, a protein kinase C inhibito r, in doses that antagonized presser responses to Ang II, but not to t he thromboxane A(2) mimic, U46619. Responses to L 163491 were not alte red by PD 123319, an AT(2) receptor antagonist. These data provide sup port for the hypothesis that vasoconstrictor responses to L 163491 are mediated by the activation of AT(1) receptors and the protein kinase C pathway in the pulmonary vascular bed of the intact-chest cat.