Effect of Adrenergic Receptor-Blocking Drugs in Pregnancy in Rats

Abstract

Although the evidence for the presence of adrenergic alpha and beta receptors in the uterus is fairly conclusive (Ahlquist, 1948; Wansbrough, Nakanishi & Wood, 1968) their significance in normal pregnancy is not known. Levy & Tozzi (1965) have demonstrated that the effect of adrenaline on the uterus could be inhibited by compounds possessing some degree of beta adrenergic receptor blocking effect. In the present investigation, the effect of administration of the beta-blocking agent, propranolol, alone, the alpha-blocking agent, dibenzyline, alone, and propranolol and dibenzyline together has been studied on implantation in three groups of normal pregnant rats. The drugs were administered on Days 1 to 4 of pregnancy in the first series of experiments and on Days 2 to 5 in the second series of experiments. The latter series of experiments was performed to ensure that the drugs were administered during the process of implantation. The number of implantation sites on Day 10 of pregnancy was observed after laparotomy. Similar studies were carried out on pregnant rats with an intra-uterine device (IUD) in one horn (Chaudhury, 1964) to see whether the anti-fertility effect of the device could be prevented by administration of beta-and alpha-blocking agents as there is some evidence that the IUD exerts its anti-fertility effect by acting on the sympathetic nerve supply to the uterus (Segal, 1964). Tables 1 and 2 show the results obtained in normal pregnant rats and in those with an IUD. The results indicate that, at the doses administered, neither propranolol, nor dibenzyline, nor simultaneous administration of both in¬ hibited pregnancy, nor did it interfere with the anti-fertility effect of the IUD. Higher doses of both drugs could not be administered as 50 mg/kg of propranolol administered simultaneously with 50 mg/kg dibenzyline was toxic. The results indicate that the sympathetic alpha and beta receptors in the rat uterus do not appear to play any significant part in normal pregnancy. Further, the effect of an IUD appeared to be present even when the alpha and beta receptors were pharmacologically blocked. M 551

Action of several β‐adrenoceptor blocking drugs in the pregnant sheep and foetus

“…Obviously, the desired pharmacological effects of these compounds are on the uterus and any effects on the foetus are undesirable and if possible, should be avoided. Sethi & Chaudhury (1970) demonstrated that a-adrenoceptor and ,p-adrenoceptor blocking drugs did not alter fertility or implantation in rats.…”