Influence of arachidonic acid metabolites on cardiac alpha 1-adrenoceptor responses in diabetic rats.
There is evidence that one or more metabolites of arachidonic acid can produce positive inotropic effects and may also be implicated in the enhanced alpha 1-adrenoceptor responses in hearts from diabetic rats. We therefore carried out a study to investigate the possibility that arachidonic acid metabolites could be involved in the altered cardiac alpha 1-effect of norepinephrine (in the presence of propranolol) in chronic streptozotocin-diabetic rats. Our results have shown that in the presence of the cyclooxygenase inhibitor indomethacin or the thromboxane synthetase inhibitor imidazole, the norepinephrine-stimulated positive inotropic effect and the formation of inositol 1,4,5-trisphosphate were significantly increased in control hearts but were unaltered in hearts from diabetic rats. The addition of the prostacyclin synthetase inhibitor tranylcypromine reduced the norepinephrine-stimulated positive inotropic effect and inositol 1,4,5-trisphosphate formation only in diabetic hearts and had no effect in the controls. The nature and physiological significance of the enhanced positive inotropic effect and inositol 1,4,5-trisphosphate formation in the control heart with the addition of indomethacin and imidazole are still unclear. The effect of tranylcypromine may indicate the participation of prostacyclin in mediating the enhanced alpha 1-inotropic effect of norepinephrine in the chronic diabetic heart.
Xiang
H
H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
McNeill
J H
JH
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007293:Inosine Triphosphate / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014191:Tranylcypromine / Q000494:pharmacology
D001095:Arachidonic Acids; D001786:Blood Glucose; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D007293:Inosine Triphosphate; D014191:Tranylcypromine; C029899:imidazole; D011433:Propranolol; D013930:Thromboxane-A Synthase; D009638:Norepinephrine