Prostaglandin H2 as an endothelium-derived contracting factor and its interaction with endothelium-derived nitric oxide.
The possibility that prostaglandin H2 is an endothelium-derived contracting factor (EDCF) was evaluated in rings of thoracic aorta of spontaneously hypertensive rats (SHR). When the aortic rings were contracted with norepinephrine (10(-7) mol/l) and treated with acetylcholine (10(-5) mol/l), a relaxant response with a peak after approximately 1 min and a contractile response with a peak after approximately 7 min were observed. When these rings were pretreated with a thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708), the later contractile response was clearly inhibited and only a sustained relaxant response was observed. This relaxant response was completely inhibited by pretreatment with an inhibitor of nitric oxide production (N-nitroarginine methylester; NNM). When aortic rings in the basal condition were treated with NNM and then with acetylcholine, a contractile response with a peak after 7 min was observed, but this reaction was completely inhibited by pretreatment with ONO-3708. The rate of 6-keto-prostaglandin F1 alpha production showed a peak of 1.4 x 10(-6) mol/l per min per tissue, 2-4 min after administration of acetylcholine. With exogenous prostaglandin H2 (5 x 10(-7) mol/l), a peak contraction was observed after approximately 4 min, the degree and pattern of which were similar to that induced by acetylcholine. Endogenous prostaglandin H2 is considered to be produced by the aortic rings in an amount sufficient to induce vascular contraction within 30 s, and the pattern of this contraction induced by acetylcholine resembles that induced by exogenous prostaglandin H2. These findings most strongly suggest that prostaglandin H2 is an EDCF.(ABSTRACT TRUNCATED AT 250 WORDS)
Ito
T
T
2nd Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kato
T
T
Iwama
Y
Y
Muramatsu
M
M
Shimizu
K
K
Asano
H
H
Okumura
K
K
Hashimoto
H
H
Satake
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism* / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D019335:Nitroarginine; D009569:Nitric Oxide; D044262:Prostaglandin H2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C049855:ONO 3708; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine