Ross Gracious R, Yallampalli Chandra
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Biol Reprod. 2007 Jan;76(1):118-23. doi: 10.1095/biolreprod.106.053777. Epub 2006 Oct 18.
Cardiovascular adaptation is a hallmark of pregnancy. Here we report on vascular hyperresponsiveness to an endogenous vasodilator, adrenomedullin (ADM), during pregnancy. Intravenous administration of ADM dose dependently decreased the mean arterial pressure, and the decrease was significantly greater in pregnant compared with nonpregnant rats without affecting the heart rate. In endothelium-intact mesenteric artery precontracted by ED70 concentration of norepinephrine, the potency and efficacy of ADM in causing the vasodilation of mesenteric arterial rings from pregnant rats are significantly higher compared with nonpregnant females at diestrus. The magnitude of inhibition of concentration-dependent response to ADM by the inhibition of either soluble guanylate cyclase or adenylate cyclase was greater in pregnant rats. Moreover, ADM-induced cyclic nucleotide generation, both cGMP and cAMP, in the mesenteric artery was elevated during pregnancy and was sensitive to the receptor antagonist, ADM22-52. These findings suggest that during pregnancy the vasodilatory effects of ADM are greater and are associated with increased generation of cyclic nucleotides in resistance vessels, and these changes may be part of the cardiovascular adaptations that occur during pregnancy.
心血管适应是妊娠的一个标志。在此，我们报告妊娠期间血管对内源性血管舒张剂肾上腺髓质素（ADM）的高反应性。静脉注射ADM可使平均动脉压呈剂量依赖性降低，且与未妊娠大鼠相比，妊娠大鼠的这种降低更为显著，同时心率不受影响。在用ED70浓度的去甲肾上腺素预收缩的内皮完整的肠系膜动脉中，与处于动情间期的未妊娠雌性大鼠相比，ADM使妊娠大鼠肠系膜动脉环舒张的效力和效能显著更高。在妊娠大鼠中，抑制可溶性鸟苷酸环化酶或腺苷酸环化酶对ADM浓度依赖性反应的抑制程度更大。此外，妊娠期间肠系膜动脉中ADM诱导的环核苷酸生成，即cGMP和cAMP，均有所升高，且对受体拮抗剂ADM22 - 52敏感。这些发现表明，在妊娠期间，ADM的血管舒张作用更强，且与阻力血管中环核苷酸生成增加有关，这些变化可能是妊娠期间发生的心血管适应的一部分。
