Modulation of vascular KATP channels in hypothyroidism

The role of vascular KATP channels in hypothyroidism-induced decrease in myogenic activity of rat portal vein was examined by using pharmacologically relevant concentrations of K+ channel ligands. As compared to controls, a significant decrease in the myogenic tone and noradrenaline (10(-9)-10(-5) M)-induced contractions was observed in portal veins from hypothyroid rats. In both euthyroid and hypothyroid states, pinacidil (10(-9)-10(-5) M) and cromakalim (10(-9)-10(-5) M) caused concentration-related inhibition of the myogenic tone (frequency and amplitude). However, hypothyroidism caused a leftward shift in the concentration-response curves of the K+ channel openers with a corresponding decrease in their IC50 values both in the absence and presence of the KATP channel blocker, glibenclamide (10(-7) M). Further, concentration-dependent increase in the frequency of myogenic tone by glibenclamide (10(-8)-3 x 10(-6) M) was greater in tissues from hypothyroid rats (EC50 = 2.07 x 10(-7) M; 95% CL, 1.06-4.05 x 10(-7) M) in comparison to controls (EC50 = 8.07 x 10(-7) M; 95% CL, 0.53-1.22 x 10(-6) M). These results suggest that a decrease in the myogenic tone of rat portal vein may possibly be related to an enhanced opening of the KATP channels in hypothyroidism.