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 m odulation by endogenous peptidases, we studied canine isolated pulmona ry arterial rings under isometric conditions in vitro. Addition of ANG II caused a concentration-dependent contraction, an effect that was n ot altered by the ANG II 2 receptor antagonist EXP655 but was depresse d by the ANG II 1 receptor antagonist DuP 753 so that the ANG II respo nse 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 sulfonylfluoride potentiated the ANG II-ind uced contraction, with the concentration required to produce a half-ma ximal 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 phosphoram idon had no effect. The p-methylphenyl sulfonylfluoride-induced potent iation was abolished by the removal of endothelium, but it was still o bserved in the presence of N-G-nitro-L-arginine methyl ester in the en dothelium-intact tissues. The PCP activity in the tissues was reduced by the removal of endothelium from 645 +/- 88 to 91 +/- 29 nmol.mg pro tein(-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 AN G II contracts pulmonary artery via ANG II 1 receptor and that PCP loc alized to the endothelium may have a modulatory role in the ANG II-ind uced pulmonary vasoconstriction.