CONSTRICTOR RESPONSES OF THE RAT BASILAR ARTERY DURING DIABETES-MELLITUS

Diabetes mellitus produces abnormalities of the endothelium and impair s endothelium-dependent dilatation of large and small cerebral blood v essels. However, the effect of diabetes mellitus on cerebral vasoconst riction and the modulatory influence of nitric oxide on cerebral vasoc onstriction is unclear. Thus, the first goal of this study was to exam ine the effect of diabetes mellitus on constrictor responses of the ba silar artery in vivo. Our second goal was to examine a potential role for nitric oxide in modulating constrictor responses of the basilar ar tery. A craniotomy was performed over the ventral medulla to expose th e basilar artery. The diameter of the basilar artery was measured usin g intravital microscopy in nondiabetic and diabetic (3-4 months after injection of streptozotocin; 50-60 mg/kg i.p.) rats in response to ang iotensin II, arginine vasopressin, endothelin-l, and the thromboxane a nalogue, U-46619. Topical application of angiotensin II (10 and 100 nM ) produced only minimal changes in diameter of the basilar artery whic h were similar in nondiabetic and diabetic rats (p > 0.05). Arginine v asopressin (0.1 and 1.0 nM), endothelin-l (10 and 50 nM), and U-46619 (10 and 100 nM) produced marked dose-related constriction of the basil ar artery which also was similar in nondiabetic and diabetic rats (p > 0.05). Next, we examine whether the synthesis/release of nitric oxide played a role in constriction of the basilar artery in response to th e agonists. Vile found that L-NMMA (1.0 mu M) did not alter constricto r responses of the basilar artery in nondiabetic and diabetic rats. Th us, responses of the basilar artery to important vasoactive agonists a re not altered by diabetes mellitus. In addition, it does not appear t hat the synthesis/release of nitric oxide modulates constrictor respon ses of the basilar artery to angiotensin II, arginine vasopressin, end othelin-l and U-46619. We suggest that preservation of vasoconstrictor responses, coupled with impaired vasodilator responses, may contribut e to the pathogenesis of cerebrovascular abnormalities associated with diabetes mellitus. (C) 1998 Elsevier Science B.V.