Role of prostaglandin H2 as an endothelium-derived contracting factor in diabetic state.

This study investigated the possible involvement of prostaglandin H2, an acetylcholine-induced endothelium-derived contracting factor in rat aorta, in the development of abnormality of the vasculature in diabetes. Rings of thoracic aorta were prepared from control Wistar-Kyoto and STZ-induced diabetic rats to examine the changes in isometric tension. In 10(-7) M norepinephrine-precontracted rings, acetylcholine induced relaxations, which were significantly impaired in diabetic rats. Inhibition of thromboxane A2-prostaglandin H2 receptors with ONO-3708 (10(-6) M) prevented the development of the impairment of relaxation in diabetic rats. Thromboxane A2 synthesis inhibition with OKY-046 (10(-5) M) did not affect the acetylcholine-induced relaxation in both control and diabetic rats. In aortic rings under resting tension, acetylcholine induced a contraction that was greater in diabetic than control rats, when the nitric oxide production was inhibited by NG-nitro-L-arginine methylester (10(-4) M). This acetylcholine-induced contraction was observed only in the rings with intact endothelium and was completely abolished by ONO-3708 (10(-6) M). The concentration of 6-keto-prostaglandin F1 alpha in the solution bathing diabetic rat aortic rings increased significantly after acetylcholine (10(-5) M) administration. Prostacyclin (10(-9)-10(-6) M) did not induce contractions at all. Prostacyclin is unlikely to mediate contractions because of its low contractile potency.(ABSTRACT TRUNCATED AT 250 WORDS)