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.
Jagadish
M
M
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, India.
Raviprakash
V
V
Telang
A G
AG
Mishra
S K
SK
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D007037:Hypothyroidism / Q000503:physiopathology*; D008297:Male; D020110:Pinacidil; D011169:Portal Vein / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil