Vascular hyperresponsiveness to adrenomedullin during pregnancy is associated with increased generation of cyclic nucleotides in rat mesenteric artery.
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.
Ross
Gracious R
GR
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Yallampalli
Chandra
C
D053607:Adrenomedullin / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D053607:Adrenomedullin; D000242:Cyclic AMP; D006152:Cyclic GMP