Effect of endothelium removal on basal and muscarinic cholinergic stimulated rat mesenteric vascular bed prostanoid synthesis.
The ability of the rat mesenteric vascular bed to synthesize prostanoids with and without endothelium in basal conditions and in response to acetylcholine (ACh) stimulation was investigated. Isolated and perfused mesenteric vascular bed released 6-keto-prostaglandin F1 alpha and thromboxane B2 (TXB2) (stable metabolites of prostacyclin (PGI2) and TXA2, respectively), and also prostaglandin E2 (PGE2) and PGF2 alpha. PGI2 was the major prostanoid formed by the mesenteric vascular bed. ACh 10(-5) M markedly increased PGI2 release without any effect on the other prostanoids. Atropine 10(-6) M added to the perfusion medium previous to ACh reduced the release of PGI2. Atropine alone did not modify the basal prostanoid pattern. Removal of endothelium with 96% ethanol produced a 50% reduction in the production of PGI2 and TXA2 with respect to basal values, without modifying PGE2 or PGF2 alpha. Cholinergic stimulation by ACh of the de-endothelialized mesenteric vascular bed significantly increased only TXA2 production. Atropine prevents this response to ACh. Our results indicate that in mesenteric vascular bed, endothelium mainly produces a potent vasodilator prostanoid, PGI2, but also a lesser proportion of TXA2. ACh, in stimulating muscarinic receptors, induces the production and release of PGI2 from endothelium and TXA2 from vascular smooth muscle when the endothelium is absent.
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Instituto de Investigaciones Farmacológicas (ININFA), Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Buenos Aires.
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D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D008643:Mesentery / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000502:physiology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
D011453:Prostaglandins; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000109:Acetylcholine