Constrictor responses of resistance arterioles during diabetes mellitus

Abstract

While diabetes mellitus appears to alter nitric oxide synthase-dependent vasodilatation, the effect of diabetes on constrictor responses of resistance arterioles is not clear. Our goal was to examine the effect of diabetes on constrictor responses of cheek pouch arterioles. In vivo diameter of arterioles (∼50 μm) was measured in response to norepinephrine, the thromboxane analogue (U-46619) and endothelin-1 in nondiabetic and diabetic hamsters (4–6 weeks post streptozotocin). Norepinephrine (1.0 and 10 nM) and U-46619 (0.1 and 1.0 nM) produced similar dose-related vasoconstriction in nondiabetic and diabetic hamsters ( P>0.05). In contrast, vasoconstriction to endothelin-1 (0.1 and 1.0 pM) was greater in diabetic than nondiabetic hamsters ( P<0.05). Next, we examined the role of nitric oxide in basal vascular tone and whether enhanced vasoconstriction in diabetic hamsters to endothelin-1 might be related to an alteration in the modulatory role of nitric oxide. N G-monomethyl- l-arginine ( l-NMMA) (1.0, 10 and 100 μM) produced dose-related vasoconstriction in nondiabetic, but not diabetic hamsters. Further, l-NMMA did not alter vasoconstriction in response to endothelin-1 in nondiabetic and diabetic hamsters. These findings suggest that diabetes alters constriction of cheek pouch resistance arterioles to endothelin-1 which appears to be independent of the synthesis/release of nitric oxide. In addition, based upon findings using l-NMMA, it appears that there is a reduced influence of nitric oxide on basal diameter of resistance arterioles during diabetes.