Pregnancy alters adrenergic mechanisms in uterine arterioles of rats

Pregnancy is associated with altered vascular reactivity. However, the effect of pregnancy on the alpha- and beta-adrenergic responses in the uterine microcirculation remains to be determined. In late-pregnant (Day 20-21, n = 6) and virgin (n = 6) Sprague-Dawley rats, uterine radial arterioles (70-120 microm in internal diameter) were isolated. We studied in vitro arteriolar responses in a pressurized, no-flow state with videomicroscopy. alpha(2)-Adrenergic activation relaxed uterine arterioles; this relaxation was increased with pregnancy and was inhibited after endothelial denudation or inhibition of nitric oxide synthase. Pregnancy significantly increased the contractile response to the alpha(1)-adrenoceptor agonist phenylephrine but decreased the relaxation to the beta-adrenoceptor agonist isoproterenol. The contractile response to the protein kinase C activator phorbol ester and relaxation responses to both the adenylate cyclase activator forskolin and the endothelium-independent cyclic guanosine monophosphate-mediated vaso- dilator nitroprusside were preserved. These results suggest that pregnancy enhances the alpha(2)-adrenoceptor-mediated relaxation of uterine arterioles, probably because of an increase in the release of nitric oxide. The alpha(1)-adrenergic response is upregulated, whereas the beta-adrenergic response is impaired, in the uterine microcirculation of pregnant rats.

Both alpha- and beta-adrenergic responses are important mechanisms for the regulation of uteroplacental perfusion. By use of an in vitromicrovascular technique, we have shown pregnancy-associated alteration in adrenergic responses in the uterine microcirculation of the rat.