Characterization of norepinephrine sensitivity in the maternal splanchnic circulation during pregnancy

Vascular sensitivity to exogenous norepinephrine and transmural nerve stimulation was studied in the splanchnic bed of nonpregnant, early pregnant, and late pregnant rats. Resistance-size mesenteric arteries were removed from late pregnant (18 to 20 days), early pregnant (7 days), and nonpregnant cycling rats and mounted in a myograph system, which permits the precise setting of vessel circumference for the determination of norepinephrine sensitivity. Norepinephrine dose-response curves and frequency-response curves for transmural nerve stimulation were obtained in the presence and absence of cocaine, a specific inhibitor of neuronal reuptake. The mesenteric arteries of late pregnant rats were 1.5 times less sensitive to exogenous norepinephrine than arteries of both early pregnant and nonpregnant rats. Sensitivity to transmural nerve stimulation was decreased in both early and late pregnant rats compared with nonpregnant controls. Cocaine potentiated the response to both exogenous norepinephrine and transmural nerve stimulation in the pregnant rats so that responses between nonpregnant, early pregnant, and late pregnant rats were no longer different. This suggests a greater reuptake activity from pregnant rats. In conclusion, pregnancy is associated with a reduction in splanchnic norepinephrine sensitivity, which may be due partly to an increase in neuronal deactivation of norepinephrine. The maximum contractile response to norepinephrine also was decreased in late pregnancy, which suggests additional mechanisms for changes in norepinephrine vascular sensitivity.