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)
Shimizu
K
K
Department of Internal Medicine II, Nagoya University School of Medicine, Japan.
Muramatsu
M
M
Kakegawa
Y
Y
Asano
H
H
Toki
Y
Y
Miyazaki
Y
Y
Okumura
K
K
Hashimoto
H
H
Ito
T
T
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D044262:Prostaglandin H2; D011453:Prostaglandins / Q000494:pharmacology; D011463:Prostaglandins H / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D011921:Rats, Inbred WKY; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014664:Vasodilation / Q000502:physiology
D016232:Endothelins; D011453:Prostaglandins; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D009569:Nitric Oxide; D044262:Prostaglandin H2; D000109:Acetylcholine; D009638:Norepinephrine