RESUMO
The mechanism by which a novel potent non-peptide angiotensin subtype 1 receptor (AT1) agonist, (5,7-dimethyl-2-ethyl-3-[[2'-[(butyloxycarbonyl) aminosulfonyl]-5'-(3-methoxybenzyl)-[1,1'-biphenyl]-4-yl] methyl]-3H-imidazo [4,5-b] pyridine) (L-163,491), increased pulmonary vascular resistance was investigated in the intact-chest anesthetized cat under conditions of controlled blood flow. Intralobar injections of L-163,491, in doses of 10-300 micrograms i.a., caused dose-related increases in lobar arterial pressure that were partially antagonized by an AT1 receptor antagonist, DuP 532, or by staurosporine, a protein kinase C inhibitor, in doses that antagonized pressor responses to Ang II, but not to the thromboxane A2 mimic, U46619. Responses to L 163491 were not altered by PD 123319, an AT2 receptor antagonist. These data provide support for the hypothesis that vasoconstrictor responses to L 163491 are mediated by the activation of AT1 receptors and the protein kinase C pathway in the pulmonary vascular bed of the intact-chest cat.
