Influence of hypothyroid state on 45Ca(2+) influx and sensitivity of rat uterus to nifedipine and diltiazem.
The influence of methimazole-induced hypothyroidism on spontaneous rhythmic contractions and Ca2+ channel function of rat uterus was examined. Hypothyroidism significantly reduced the amplitude and frequency of spontaneous rhythmic contractions. Nifedipine (10(-12)-10(-6) M) and diltiazem (10(-9)-10(-4) M) caused concentration-related inhibition of the myogenic responses of the oestrogenised rat uterus obtained from both eu- and hypothyroid rats. However, nifedipine was less potent (IC(50); 5.4 x 10(-9) M; n=6) in hypothyroid rat uterus as compared to euthyroid controls (IC(50): 8.13 x 10(-12) M; n=9) to inhibit the rhythmic contractions. Similarly, diltiazem was less potent (IC(50): 4.57 x 10(-6) M; n=9) to inhibit the uterine spontaneous contractions in hypothyroid than in euthyroid rat uterus (IC(50): 6.4 x 10(-8) M; n=6). A similar decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100 mM)-induced tonic contraction was observed in uterus obtained from hypothyroid rats compared to the controls. Both nifedipine and diltiazem were less potent for causing concentration-related inhibition of K+-stimulated 45Ca2+ influx in uterine strips taken from the hypothyroid rats. Thus, the IC(50) values of nifedipine (1.83 x 10(-8) M; n=12) and diltiazem (1.8 x 10(-6) M; n=9) were significantly greater in tissues obtained from hypothyroid rats compared to the controls (IC(50) of nifedipine, 1.15 x 10(-11) M; n=12, diltiazem, 8.1 x 10(-8) M; n=8). Nifedipine-sensitive influx of 45Ca2+ - stimulated either by K+ (100 mM) or Bay k8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2'-(trifluromethyl)phenyl]-3-pyridine carboxylic acid methyl ester) (10(-8) M) was significantly less in uterine strips from hypothyroid rats compared to the controls. The results of the present study 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
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243122 (UP), India.
Raviprakash
V
V
Telang
A G
AG
Varshney
V P
VP
Mishra
S K
SK
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D008713:Methimazole / Q000008:administration & dosage; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013974:Thyroxine / Q000097:blood / Q000187:drug effects; D014284:Triiodothyronine / Q000097:blood / Q000187:drug effects; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D014284:Triiodothyronine; D008713:Methimazole; D004110:Diltiazem; D009543:Nifedipine; D013974:Thyroxine; D002118:Calcium