title: Prostacyclin, its fatty acid precursor and its metabolites on the inotropic function of and on the prostanoid generation by diabetic arteries.
abstract: Relationships between arachidonic acid (AA) metabolism and contractile responses to Na arachidonate (NaA) to prostacyclin (PGI2) and to some of its metabolites, in mesenteric arteries, isolated from sham operated and from diabetic, totally pancreatectomized dogs; were studied. Arachidonate and prostacyclin enhanced the resting basal tone of preparations from pancreatectomized animals but depressed it in vessels from intact normal controls or from sham operated dogs. Inhibitors of thromboxane A2 (TXA2) biosynthesis, abolished in vitro the vasoconstring effect of NaA and PGI2 in diabetics; whereas inhibitors of PGI2 biosynthesis blocked the vasodilating influence of NaA in normal mesenterics. Additionally, antagonists of cyclooxygenase activity precluded both, the vasoconstricting and vasodilating actions of NaA in normal and in diabetic arteries, respectively, as well as the PGI2 tone enhancement in vessels from diabetics. Blockers of adrenoreceptors and antagonists of lipoxygenases, failed to block the positive inotropic effects of PGI2 in mesenterics from diabetic dogs. On the other hand, 6-keto-PGF1 alpha did not evoke contractile influences, either in diabetics or in controls, whereas 6-keto-PGE1 induced, in both groups, a dose-dependent relaxation. In arteries from pancreatectomized animals treated with insulin, PGI2 induced a biphasic effect (constriction and relaxation) of magnitudes between those seen in normal controls or sham operated and, in untreated diabetics. The basal radioconversion of exogenous [1-14C]-AA, evidenced that mesenterics from diabetic animals generated more TXB2 than vessels from intact normal control or from sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D015232:Dinoprostone; D004285:Dogs; D007328:Insulin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000502:physiology / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D010180:Pancreatectomy; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001095:Arachidonic Acids; D007328:Insulin; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; C022950:6-ketoprostaglandin E1; D000527:Alprostadil; D015232:Dinoprostone