PROSTAGLANDIN-H2 AS AN ENDOTHELIUM-DERIVED CONTRACTING FACTOR AND ITS INTERACTION WITH ENDOTHELIUM-DERIVED NITRIC-OXIDE

The possibility that prostaglandin H-2 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 H-2 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 H-2 (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 H-2 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 H-2. These findings most strongly suggest that prostaglandin H-2 is an EDCF. It is also suggested that, in the rat aorta treated by acetylcholine, the vascular tonus is regulated by two factors, i.e. EDCF (prostaglandin H-2) and endothelium-derived relaxing factor (nitric oxide).