Hyperreactivity of coronary vasculature in platelet-perfused hearts from diabetic rats.
Coronary vascular responsiveness to platelet-produced eicosanoids was examined in isolated perfused hearts of alloxan-diabetic rats. Coronary perfusion pressure was increased in isolated hearts of control and diabetic rats on perfusion with platelets and arachidonic acid (AA). However, the increase in perfusion pressure was approximately twofold higher in hearts of diabetic rats when compared with those isolated from control rats. This was associated with increased thromboxane B2 (TxB2) and prostaglandin F2 alpha (PGF2 alpha) production that was comparable in platelet-perfused hearts of control and diabetic animals. Ibuprofen, a cyclooxygenase inhibitor, blocked the increase in perfusion pressure and TxB2 and PGF2 alpha production by greater than 90% in both control and diabetic hearts perfused with platelets and AA. Dazoxiben, a thromboxane synthetase inhibitor, blocked the increase in perfusion pressure by 50%, totally inhibited TxB2 production, but increased PGF2 alpha production by 60% in both groups of platelet-perfused hearts. Increased levels of PGF2 alpha and possibly other constrictor eicosanoids (e.g., leukotriene D4) may account for the partial constriction observed in platelet-perfused hearts with dazoxiben. Results of the present study suggest that vascular reactivity to vasoconstrictor eicosanoids is increased in hearts of diabetic animals.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D007052:Ibuprofen / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D011453:Prostaglandins / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D007093:Imidazoles; D011453:Prostaglandins; C029166:dazoxiben; D016718:Arachidonic Acid; D013930:Thromboxane-A Synthase; D007052:Ibuprofen