Analysis of angiotensins I, II, and III in pulmonary vascular bed of the rat.
The inhibitory effects of losartan (Dup 753), a nonpeptide angiotensin (ANG) II-type 1 receptor antagonist, on responses to ANG I, II, and III were investigated in the isolated perfused lung of the rat. Under conditions of constant pulmonary blood flow and left atrial pressure, injections of ANG I, II, and III into the pulmonary arterial perfusion circuit caused dose-related increases in pulmonary arterial pressure. Responses to ANG I, II, and III were reproducible with respect to time, and Dup 753, in a dose of 3 nM/ml injected into the perfusion circuit, decreased responses to the three peptides. Dup 753 had no significant effect on pressor responses to norepinephrine, serotonin, or BAY K 8644, and Dup 753 had no significant effect on mean baseline pulmonary arterial or airway pressure. Captopril and enalaprilat, ANG II-converting enzyme inhibitors, decreased the pressor response to ANG I while increasing the pressor response to ANG II and III. In addition, responses to ANG I, II, and III were similar when compared on a molar basis, suggesting the three peptides had similar pressor activity in the isolated perfused rat lung. Pressor responses to the angiotensin peptides were greater compared with responses to pressor agents that increase vascular resistance by various mechanisms, and Dup 753 did not significantly alter the pressor response to ventilatory hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Nossaman
B D
BD
Department of Anesthesiology, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699.
Feng
C J
CJ
Wang
J
J
Kadowitz
P J
PJ
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000805:Angiotensin III / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000805:Angiotensin III; D000803:Angiotensin I; D002216:Captopril; D015773:Enalaprilat; D019808:Losartan