Anesth Pain Med.  2019 Oct;14(4):429-433. 10.17085/apm.2019.14.4.429.

The relaxant effect of nicardipine on the isolated uterine smooth muscle of the pregnant rat

Affiliations
  • 1Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju, Korea. mdmole@chosun.ac.kr
  • 2Department of Anesthesiology and Pain Medicine, Chosun University School of Medicine, Gwangju, Korea.

Abstract

BACKGROUND
Nicardipine, a calcium channel blocker, is used to treat hypertension in pregnancy or preterm labor. The current study was conducted to investigate the relaxant effects of nicardipine on the isolated uterine smooth muscle of the pregnant rat.
METHODS
We obtained uterine smooth muscle strips from pregnant female SD rats. After uterine contraction with oxytocin 10 mU/ml, we added nicardipine (10⁻¹² to 10⁻⁸ M) accumulatively every 20 min. We recorded active tension and frequency of contraction, and calculated ECâ‚… (effective concentration of 5% reduction), ECâ‚‚â‚…, ECâ‚…â‚€, EC₇₅, and EC₉₅ of active tension and frequency of contraction using a probit model.
RESULTS
Nicardipine (10⁻¹² to 10⁻⁸ M) decreased active tension and frequency of contraction in a concentration-dependent manner. The ECâ‚…â‚€ and EC₉₅ of nicardipine in the inhibition of active tension of the uterine smooth muscle were 2.41 × 10⁻¹â° M and 3.06 × 10⁻⁷ M, respectively. The ECâ‚…â‚€ and EC₉₅ of nicardipine in the inhibition of frequency of contraction of the uterine smooth muscle were 9.04 × 10⁻¹¹ and 4.18 × 10⁻⁷ M, respectively.
CONCLUSIONS
Nicardipine relaxed and decreased the frequency of contraction of the uterine smooth muscle in a concentration-dependent pattern. It might be possible to adjust the clinical dosage of nicardipine in the obstetric field based on our results, but further clinical studies are needed to confirm them.

Keyword

Nicardipine; Rat; Relaxation; Smooth muscle; Uterine contraction; Uterus

MeSH Terms

Animals
Calcium Channels
Female
Humans
Hypertension
Muscle, Smooth*
Nicardipine*
Obstetric Labor, Premature
Oxytocin
Pregnancy
Rats*
Relaxation
Uterine Contraction
Uterus
Calcium Channels
Nicardipine
Oxytocin

Figure

  • Fig. 1 Probability of inhibition of active tension of the pregnant rat uterine smooth muscle according to the concentration of nicardipine (M). Horizontal bars show 95% confidence interval for the efficient concentration of nicardipine in reducing contractility of uterine smooth muscle as 50% and 95% of probabilities (EC50 and EC95), respectively. EC: effective concentration.

  • Fig. 2 Probability of inhibition of the frequency of contraction in the pregnant rat uterine smooth muscle according to the concentration of nicardipine (M). Horizontal bars show 95% confidence interval for the efficient concentration of nicardipine in reducing contractility of uterine smooth muscle as 50% and 95% of probabilities (EC50 and EC95), respectively. EC: effective concentration.


Reference

1. Sorkin EM, Clissold SP. Nicardipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in the treatment of angina pectoris, hypertension and related cardiovascular disorders. Drugs. 1987; 33:296–345. DOI: 10.2165/00003495-198733040-00002. PMID: 3297616.
2. Nij Bijvank SW, Duvekot JJ. Nicardipine for the treatment of severe hypertension in pregnancy:a review of the literature. Obstet Gynecol Surv. 2010; 65:341–7. DOI: 10.1097/OGX.0b013e3181e2c795. PMID: 20591204.
3. Gáspár R, Hajagos-Tóth J. Calcium channel blockers as tocolytics:principles of their actions, adverse effects and therapeutic combinations. Pharmaceuticals (Basel). 2013; 6:689–99. DOI: 10.3390/ph6060689. PMID: 24276256. PMCID: PMC3816733.
4. Wray S. Uterine contraction and physiological mechanisms of modulation. Am J Physiol. 1993; 264(1 Pt 1):1–18. DOI: 10.1152/ajpcell.1993.264.1.C1. PMID: 8430759.
5. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG. National Centre for the Replacement, Refinement and Reduction of Amimals in Research. Animal research:reporting in vivo experiments--the ARRIVE guidelines. J Cereb Blood Flow Metab. 2011; 31:991–3. DOI: 10.1038/jcbfm.2010.220. PMID: 21206507. PMCID: PMC3070981.
6. Chung CD, An TH, Jung KT, Lee TH. The effects of etomidate on the contraction of pregnant rat uterine smooth muscle. Korean J Anesthesiol. 2009; 57:84–7. DOI: 10.4097/kjae.2009.57.1.84. PMID: 30625835.
7. Lee SI, Hwang GB, Baik CY. The relationship of the estimates of effective concentration calculated by logit, probit, and sigmoid emax. Korean J Anesthesiol. 2002; 43:345–7. DOI: 10.4097/kjae.2002.43.3.345.
8. Bursztyn L, Eytan O, Jaffa AJ, Elad D. Mathematical model of excitation-contraction in a uterine smooth muscle cell. Am J Physiol Cell Physiol. 2007; 292:1816–29. DOI: 10.1152/ajpcell.00478.2006. PMID: 17267547.
9. Arrowsmith S, Wray S. Oxytocin:its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol. 2014; 26:356–69. DOI: 10.1111/jne.12154. PMID: 24888645.
10. Carbonne B, Jannet D, Touboul C, Khelifati Y, Milliez J. Nicardipine treatment of hypertension during pregnancy. Obstet Gynecol. 1993; 81:908–14. PMID: 8497354.
11. Bartels PA, Hanff LM, Mathot RA, Steegers EA, Vulto AG, Visser W. Nicardipine in pre-eclamptic patients:placental transfer and disposition in breast milk. BJOG. 2007; 114:230–3. DOI: 10.1111/j.1471-0528.2006.01200.x. PMID: 17166219.
12. Curran MP, Robinson DM, Keating GM. Intravenous nicardipine:its use in the short-term treatment of hypertension and various other indications. Drugs. 2006; 66:1755–82. DOI: 10.2165/00003495-200666130-00010. PMID: 16978041.
13. Ducsay CA, Thompson JS, Wu AT, Novy MJ. Effects of calcium entry blocker (nicardipine) tocolysis in rhesus macaques:fetal plasma concentrations and cardiorespiratory changes. Am J Obstet Gynecol. 1987; 157:1482–6. DOI: 10.1016/S0002-9378(87)80248-X. PMID: 3425651.
14. Doret M, Mellier G, Gaucherand P, Saade GR, Benchaib M, Fru-toso J, et al. The in vitro effect of dual combinations of ritodrine, nicardipine and atosiban on contractility of pregnant rat myometrium. BJOG. 2003; 110:731–4. DOI: 10.1111/j.1471-0528.2003.02443.x. PMID: 12892684.
15. Serena C, Begot E, Cros J, Hodler C, Fedou AL, Nathan-Denizot N, et al. Nicardipine-induced acute pulmonary edema:a rare but severe complication of tocolysis. Case Rep Crit Care 2014. 2014; 242703. DOI: 10.1155/2014/242703. PMID: 25215245. PMCID: PMC4156995.
Full Text Links
  • APM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr