Open Access Open Access  Restricted Access Subscription Access
Cover Image

Effects of in- utero exposure to oral nifedipine and labetalol on some reproductive indices in hypertensive pregnant wistar rats

O. Onaadepo, K. V. Olorunshola, Y. Tanko


Thestudy investigated the effects of in utero exposure to oral nifedipine andlabetalol on some reproductive indices in hypertensive pregnant wistar rats. Thirty(30) pregnant female rats were randomly divided into six (6) groups of five (5)rats each and were treated as follows: Group 1: Normotensive pregnant controlrats, Group 2:  Normotensive pregnantrats + 51.1mg/kg b w of Nifedipine, Group 3: Normotensive pregnant rats + 2.5mg/kg b w of Labetalol, Group 4:Hypertensive pregnant control rats, Group 5: Hypertensive pregnant rats +51.1mg/kg b w of Nifedipine and Group 6: Hypertensive pregnant rats + 2.5 mg/kgb w of Labetalol. Hypertension was induced in rats by using 8% sodium chlorideadded to their regular feeds for a period of eight weeks. The female rats weremated with fertile male rats in a ratio of 2:1. Treatment was given orally toanimals once daily throughout gestation period in all groups till ten (10) dayspostpartum. At the end of treatment, reproductive indices were calculated andall animals from each group were sacrificed at postnatal day 10 and the uteriwere excised and stained in few drops of 10% ammonium sulphide for ten (10)minutes to determine the implantation sites and post implantation losses. Theresults obtained revealed that the correlation of the implantation site withthe litter size indicated that post implantation loss of 9% recorded from ratsin the normotensive pregnant control group wassignificantly lower than the nifedipine (51.1mg/kg bw) and labetalol (2.5mg/kg b w) treated normotensivepregnant rats which had 25% and 45% post implantation lossesrespectively with labetalol (2.5mg/kg bw) treated normotensivepregnant group recording the highest post implantation loss. On theother hand, 11.1% of post implantation loss was also recorded from rats in the hypertensive pregnant control group which wassignificantly lower than the nifedipine (51.1mg/kg bw) and labetalol (2.5mg/kg b w) treated hypertensive pregnant animalswhich recorded 22.5% and 30.0% post implantation loss. It can be concluded thatthese anti-hypertensivedrugs may be involved in large percentage of implantation losses especially insubject with pre-existing or chronic hypertension in pregnancy that may requirethe drugs throughout gestation.


Abel, M.H., Hollinsworth, M.S., 1986. Comparison of nifedipine and diltazem with salbutamol for prevention of preterm delivery in the ovariectomized oestrogen treated late pregnant rat. J. Reprod. Fert., 77, 559-568.

Brown, M.A., Buddie, M.L., Farrel, T., Davis, G.K., 2002. Efficacy and safety of nifedipine tablets for the acute treatment of severe hypertension in pregnancy. American journal of obstetrics and gynaecology ;187,1046-50.

Brown, M.A., Hague, W.M., Higgins, J., Lowe, S., McCowan, L., Oats, J., Peek, M.J., Rowan, J.A., Walters, B.N.,2000. The detection, investigation and management of hypertension in pregnancy: full consensus statement . Austrialian and New Zealand Journal of Obstetrics and Gynaecology. 40,139-155.

Butter, H,S.,1996. An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Molecular cellular Biochemistry;176, 61-71.

Harake, B., Gilbert, R.D., Ashwall, S., Power G.G.,1987. Nifedipine: effects on fetal an maternal hemodynamics in pregnant sheep. American Journal of Obstetrics and Aynaecology 157, 1003–1008.

Holbrook, R.H.,1989. Effects of calcium antagonists during pregnancy. American Journal of Obstetrics and Gyneacology ;160,1018.

Katzung, B. G.,2006. Basic and clinical pharmacology. New York: McGraw-Hill Medical. P.170. ISBN 0-07-145153-6.

Limas, C., Goldman,. P.,1981.Effect of salt loading in hypertension prone and resistant dahl Rats .Hypertension vol 3, 212-224.

Magee, L.A., Schick,B., Donnenfeld, A.E., Sage, S.R., Conover, B., Cook, L., McElhatton, P.R., Schmidt, M.A., Koren,G.,1996. The safety of calcium channel blockers in human pregnancy: a prospective multicentre cohort study. American journal of obstetrics and gynaecology 174,823-828.

Ojo, O.A.,Briggs, E.B.,1992. A textbook for midwives in the tropics 2nd edn. Ghana Gibrine publication.

Pfizer, 2007. Pfizer Material Safety Data Sheet. Revision date: 18-Jul-2007 Pp1-7.

Podymow,T., August, P.,2008. Updates on the use of Antihypertensive in pregnancy, American Heart Association: 51; 960.

Salewski, E., 1964. Färbemethode zum makroskopischen Nachweis von Implantations-stellen am Uterus der Ratte. Arch. Exp. Pathol. Pharmakol. 247, 367.

United State Environmental Protection Agency, 1996. Guidelines for Reproductive Toxicity Risk Assessment. Fed. Reg. 61(212), 56274-56322

Full Text: PDF


  • There are currently no refbacks.