Cyclooxygenase inhibition corrects the impaired microvascular reactivity in diabetic female rats

Several studies have shown that endothelium-dependent vascular relaxation is altered in experimental diabetes and in diabetic patients, with peripheral vascular disease being almost twice as frequent in diabetic women as compared with diabetic men. Moreover, the mesenteric microvessels exhibit impaired responses to acetylcholine, bradykinin, histamine, and platelet activator factor in diabetic female rats. The aim of the present study was to investigate the effects of inhibition of cyclooxygenase upon the reduced response to endothelium-dependent vasodilator agents in diabetic female rats, to verify the possible involvement of prostaglandins in that alteration. The changes of arteriolar and venular diameter after topical application of acetylcholine (17 nmol), bradykinin (30 pmol), and histamine (2.7 nmol) were measured in vivo by means of a closed video circuit coupled to a microscope before and after acute treatment with diclofenac, a cyclooxygenase inhibitor (2.5 mg/kg, intramuscularly). The cyclooxygenase inhibition corrected the decreased response of arterioles and venules to bradykinin, but only corrected the decreased venular response to acetylcholine. Diabetes impaired the response to histamine in arterioles but not in venules, and that response reduction was also corrected by diclofenac (see Table 1). These data suggest that increased release of vasoconstrictor prostanoids may be involved in the impaired response to endothelium-dependent vasodilator agents in diabetic female rats.

Table 1