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The effects of long‐term infusion of salbutamol, diltiazem and nifedipine on uterine contractions in the ovariectomized, post‐partum rat
Author(s) -
Abel Margaret H.,
Hollingsworth M.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10238.x
Subject(s) - salbutamol , nifedipine , diltiazem , uterus , medicine , bolus (digestion) , tocolytic , ovariectomized rat , anesthesia , endocrinology , estrogen , calcium , pregnancy , gestation , preterm labor , biology , asthma , genetics
1 The sensitivity of the uterus to the inhibition of contractions by salbutamol, diltiazem or nifedipine was assessed in the ovariectomized, post‐partum rat by dose‐response curves following bolus intravenous (i.v.) administration. These tests were performed before (day 1), immediately after a 20 h i.v. infusion of salbutamol, diltiazem, nifedipine or appropriate control infusate (day 2) and after a further 20 h infusion of saline (day 3). In a further group of animals sensitivity to nifedipine was assessed before and after a 20 h infusion of salbutamol. Uterine contractions were monitored throughout infusions. 2 Infusion of salbutamol (2 μg kg −1 min −1 ) produced an initial marked inhibition of uterine contractions, an effect which was not maintained despite continued infusion. Contractions reappeared after 2 h of infusion and reached pre‐infusion levels by 5 h. The dose‐response curve to salbutamol on day 2 was shifted more than 100 fold to the right compared with that on day 1. Sensitivity of the uterus on day 3 did not differ from that on day 1. 3 Nifedipine (25 μg kg −1 min −1 ) produced sustained inhibition of uterine contractions throughout the 20 h of infusion. Sensitivity of the uterus to nifedipine could not, therefore, be tested on day 2; sensitivity on day 3 did not differ from that on day 1. In addition, there was no change in sensitivity of the uterus to nifedipine after a 20 h infusion of salbutamol. 4 Diltiazem (200 μg kg −1 min −1 ) produced a marked initial inhibition of uterine contractions, with a partial return of contractions during continued infusion in 7 out of 12 animals so that mean integral values reached 40% of those pre‐infusion. The dose‐response curve to diltiazem on day 2 showed a 25 fold shift to the right compared with that on day 1 in 4 out of 12 animals where the test could be performed. Sensitivity of the uterus on day 3 did not differ from that on day 1. 5 These findings suggest that marked but reversible tolerance to the inhibitory actions of salbutamol on uterine contractions occurs during long‐term infusion. There was no evidence of tolerance to the uterine actions of nifedipine, but there was evidence of tolerance to diltiazem in some animals. 1