Beneficial effect induced by a beta-adrenoceptor blocker on fetal growth in streptozotocin-diabetic rats.

Abstract

Treatment by a beta 1-beta 2-adrenoceptor antagonist has been much used during pathological pregnancies. These agents can reduce the oxygen consumption of the myocardium, increase the coronary blood flow towards ischemic heart areas and improve return of venous blood flow towards the heart. The aim of this study was to determine the mechanism of action of this agent and to investigate whether a total beta-adrenoceptor antagonist could reduce the fetoplacental disorders elicited in streptozotocin-diabetic pregnant rats. Diabetes was engendered on day 7.5 of pregnancy, and the animals were studied on day 21. Untreated nondiabetic rats or nondiabetic rats treated with propranolol, a total beta-adrenoceptor blocker (2 mg kg-1/ day, i.p.), had a healthy placenta without vascular disturbances, with normal arterial blood velocity in the uterine artery, placenta, umbilical cord and fetal aorta, and showed eutrophic fetuses (3.9 +/- 0.0 g, mean +/- SEM). Untreated diabetic rats had severe placental lesions, with a reduction of arterial blood velocity in the uterine artery (p < 0.01), placenta (p < 0.01) and umbilical artery (p < 0.05), and exhibited fetal hypotrophy (2.3 +/- 0.1 g, mean +/- SEM, p < 0.001) compared with nondiabetic untreated rats. Treatment of diabetic rats with propranolol (2 mg kg-1/day, i.p.) enhanced fetal weight (3.66 +/- 0.2 g) and slightly increased fetal insulin secretion, restored arterial blood velocity to control values in the uterine artery and fetal aorta and reduced placental lesions. In conclusion, our results suggest that the beneficial effects of propranolol were at least in part related to an improvement of uteroplacental hemodynamics; it induced a better redistribution of the blood towards the placenta and the fetal systemic circulation. Propranolol treatment could protect cell membranes against free oxygen radicals and lipid peroxidation, involved in the pathogenesis of ischemic injury in diabetes.