Angiotensin II 1 receptor-mediated contraction of pulmonary artery and its modulation by prolylcarboxypeptidase.
To determine the subtype of angiotensin II (ANG II) receptor involved in the contraction of pulmonary artery and to elucidate its possible modulation by endogenous peptidases, we studied canine isolated pulmonary arterial rings under isometric conditions in vitro. Addition of ANG II caused a concentration-dependent contraction, an effect that was not altered by the ANG II 2 receptor antagonist EXP655 but was depressed by the ANG II 1 receptor antagonist DuP 753 so that the ANG II response curves were displaced to higher concentration by 1.5-2.0 log U (P < 0.001). Pretreatment of tissues with the prolylcarboxypeptidase (PCP) inhibitor p-methylphenyl sulfonyl-fluoride potentiated the ANG II-induced contraction, with the concentration required to produce a half-maximal effect of ANG II being decreased from 4.1 +/- 0.9 x 10(-9) to 3.8 +/- 0.5 x 10(-10) M (P < 0.001), whereas other peptidase inhibitors such as p-chloromercuriphenyl sulfonic acid, amastatin, and phosphoramidon had no effect. The p-methylphenyl sulfonylfluoride-induced potentiation was abolished by the removal of endothelium, but it was still observed in the presence of NG-nitro-L-arginine methyl ester in the endothelium-intact tissues. The PCP activity in the tissues was reduced by the removal of endothelium from 645 +/- 88 to 91 +/- 29 nmol.mg protein-1.h-1 (P < 0.001), and cultured endothelium had the activity of 404 +/- 39 nmol.mg protein-1.h-1. These results suggest that ANG II contracts pulmonary artery via ANG II 1 receptor and that PCP localized to the endothelium may have a modulatory role in the ANG II-induced pulmonary vasoconstriction.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Sugimoto
F
F
Tagaya
E
E
Isono
K
K
Chiyotani
A
A
Konno
K
K
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011480:Protease Inhibitors; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D009569:Nitric Oxide; D001120:Arginine; D002268:Carboxypeptidases; C022448:lysosomal Pro-X carboxypeptidase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester