Pharmacological modulation of bradykinin-, acetylcholine- and calcium ionophore A23187-induced relaxation of rabbit pulmonary arterial segments.
Bradykinin (BK; 10(-10)-10(-7) M) relaxes phenylephrine-contracted rabbit isolated pulmonary arterial rings. The mechanical destruction of the endothelial layer obliterates acetylcholine (ACh) and A23187-induced relaxation without influencing BK-, isoproterenol-, sodium nitroprusside- and papaverine-induced relaxations. Atropine and propranolol selectively antagonized ACh- and isoproterenol-induced relaxation, respectively, without influencing BK-induced relaxation. Indomethacin (1.4 X 10(-5) M, a potent cyclooxygenase inhibitor, 30-60 min) and p-bromophenacylbromide (5 X 10(-6) M, p-BPB, a potent phospholipase A2 inhibitor, 30-60 min) selectively inhibited BK-induced relaxation without influencing relaxation to isoproterenol, sodium nitroprusside and papaverine. These data suggest that BK stimulates PLA2 and releases arachidonic acid (AA), which is further metabolized via cyclooxygenase and prostaglandin synthetase to prostacyclin (PGI2), causing relaxation of rabbit pulmonary arterial segments. The inhibition of ACh- and A23187-induced relaxation by p-BPB, but not by indomethacin, suggest that initial activation of PLA2 causes the release of AA, which is subsequently metabolized to endothelial-derived relaxant factor (EDRF; lipid peroxides, ROOH, ROO-?).
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D010656:Phenylephrine; D000001:Calcimycin; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin