CORRELATION WITH BLOOD-PRESSURE OF THE ACETYLCHOLINE-INDUCED ENDOTHELIUM-DERIVED CONTRACTING FACTOR IN THE RAT AORTA

To examine a relation between the production of acetylcholine-induced endothelium-derived contracting factor and an increase in blood pressure, endothelium-dependent contraction and relaxation were evaluated by measuring the isometric tension of aortic rings from spontaneously hypertensive rats and Wistar-Kyoto rats at 5, 10, 20, and 30 weeks of age. In norepinephrine-precontracted rings, acetylcholine (10(-8) to 10(-5) M)-induced relaxations diminished at the doses of 10(-6) to 10(-5) M in both strains except at 5 weeks of age. Treatment with a thromboxane A2/prostaglandin H-2 antagonist (ONO-3708) prevented this reduction in acetylcholine-induced relaxations in both strains and induced dose-dependent relaxations, which were completely inhibited by treatment with a nitric oxide inhibitor, N(G)-nitro-L-arginine methyl ester. In aorta treated with N(G)-nitro-L-arginine methyl ester without precontraction, acetylcholine induced dose-dependent contractions, which were greater in spontaneously hypertensive rats than in Wistar-Kyoto rats. These acetylcholine-induced contractions, which were observed only in rings with endothelium, were completely inhibited by treatment with ONO-3708 but not with a thromboxane A2 synthetase inhibitor (OKY-046). There was a statistically significant correlation between the acetylcholine-induced contractions and blood pressure. Release of 6-ketoprostaglandin F1-alpha by acetylcholine from the aorta was greater in spontaneously hypertensive rats. In vivo administration of another thromboxane A2/prostaglandin H-2 antagonist (ONO-8809) (10 or 30-mu-g per body per day) for 3 weeks (5-8 weeks of age) did not affect blood pressure in either rat strain. These results suggest that the production of acetylcholine-induced endothelium-derived contracting factor, which is most likely prostaglandin H-2, is closely associated with the increase in blood pressure that occurs in young to adult rats.