Hypothyroid state reduces calcium channel function in 18-day pregnant rat uterus.
Hypothyroidism significantly reduced the mean amplitude and increased the mean frequency of spontaneous rhythmic contractions in 18 day pregnant rat uterus. Nifedipine (10(-12)-10(-9) M) and diltiazem (10(-10)-10(-6) M) 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 x 10(-11) M) in pregnant hypothyroid state as compared to pregnant control (IC50: 3.1 x 10(-12) M). Similarly, diltiazem was less potent (IC50: 3.72 x 10(-9) M) in inhibiting the uterine spontaneous contractions in hypothyroid than in pregnant rat uterus (IC50:5.37 x 10(-10) M). A similar decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100 mM)-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 45Ca(2+)-stimulated either by K+ (100 mM) or by Bay K8644 (1,4-dihydro-2,6-methyl-5-nitro-4-[2'-(trifluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10(-9) M) 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.
Parija
S C
SC
Department of Pharmacology and Toxicology, College of Veterinary Science & Animal Husbandry, Bhubaneswar 751 003, India. scp4691@yahoo.co.in
Mishra
S K
SK
Raviprakash
V
V
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D007037:Hypothyroidism / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D008713:Methimazole / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013963:Thyroid Hormones; D008713:Methimazole; D004110:Diltiazem; D009543:Nifedipine