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 (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.
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000819:agonists*; D019311:Staurosporine; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000470:Alkaloids; D004791:Enzyme Inhibitors; D007093:Imidazoles; C096715:L 163491; D011725:Pyridines; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011493:Protein Kinase C; D019311:Staurosporine