Hypothyroid state reduces calcium channel function in 18-day pregnant rat uterus

Abstract

Hypothyroidism significantly reduced the mean amplitude and increased the mean frequency of spontaneous rhythmic contractions in 18day pregnant rat uterus. Nifedipine (10^-12-10^-9 <i style="">M</i>) and diltiazem (10^-10-10^-6<i style="">M</i>) caused concentration related inhibition of the myogenic responses of the uterine strips obtained from both pregnant and hypothyroid state. However, nifedipine was less potent (IC₅₀:2.11×10^-11 <i style="">M</i>) in pregnant hypothyroid state as compared to pregnant control (IC₅₀: 3.1×10^-12<i style="">M</i>). Similarly, diltiazem was less potent (IC₅₀ : 3.72×10^-9<i style="">M</i>) in inhibiting the uterine spontaneous contractions in hypothyroid than in pregnant rat uterus (IC₅₀:5.37×10^-10 M). A similar decrease in the sensitivity to nifedipine and diltiazem for reversal of K⁺(100 m<i style="">M</i>)–induced tonic contraction and K⁺-stimulated ⁴⁵Ca²⁺ influx was observed with these calcium channel antagonists in uterus obtained from hypothyroid pregnant rats compared to the controls. Nifedipine–sensitive influx of ⁴⁵Ca²⁺-stimulated either by K⁺ (100 m<i style="">M</i>) or by Bay K8644 (1,4-dihydro-2,6-methyl-5-nitro-4-[2'-(tri-fluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10^-9 <i style="">M</i>) was significantly less in uterine strips from hypothyroid rats compared to controls. The results suggest that the inhibition of uterine rhythmic contractions may be attributable to a reduction in rat myometrial Ca²⁺channel function in the hypothyroid state.<b style=""></b>