Comparison of pressor responses to angiotensin I, II, and III in pulmonary vascular bed of cats.
Pulmonary vascular responses to angiotensin (ANG) peptides were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. Intralobar injections of ANG I, II, and III caused dose-related increases in lobar arterial pressure, whereas ANG (1-7) and ANG (3-8) (ANG IV) had modest pressor activity. ANG I, II, and III had similar activity and were more potent than norepinephrine and ANG (1-7) and ANG IV but less potent than the thromboxane A2 mimic, U-46619, in increasing lobar arterial pressure. The time course of responses to ANG I, II, and III was similar, and after administration of ANG receptor antagonists, DuP 532 and L-158,809, responses to ANG I, II, and III was reduced, whereas responses to norepinephrine, serotonin, and U-46619 were not altered. After administration of the ANG-converting-enzyme inhibitor, captopril, responses to ANG I were reduced. The converting-enzyme inhibitor enhanced pressor responses to ANG II and III but did not alter responses to norepinephrine, U-46619, or serotonin. Moreover, under elevated-tone conditions, pulmonary vasodilator responses to bradykinin were increased following administration of captopril, whereas vasodilator responses to acetylcholine and nitrovasodilators were not altered. These results demonstrate that ANG I, II, and III have similar pulmonary pressor activity and that responses are mediated by ANG II type 1 receptors. Pressor responses to ANG I are reduced, whereas vasodilator responses to bradykinin are enhanced by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
D Y
DY
Cheng
B J
BJ
DeWitt
T J
TJ
McMahon
P J
PJ
Kadowitz
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D002415:Cats; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D005466:Fluorocarbons
D000803:Angiotensin I; D000804:Angiotensin II; D000805:Angiotensin III; D057911:Angiotensin Receptor Antagonists; D002216:Captopril; D007093:Imidazoles; D013777:Tetrazoles; C069045:DuP 532; D005466:Fluorocarbons; C070967:L 158809