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Vascular Hyperresponsiveness to Adrenomedullin During Pregnancy Is Associated with Increased Generation of Cyclic Nucleotides in Rat Mesenteric Artery¹

Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555

ABSTRACT

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, ADM_22–52. 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.

adrenomedullin, blood pressure, cyclic adenosine monophosphate, cyclic guanosine monophosphate, cyclic nucleotides, pregnancy, vascular relaxation

¹Supported wholly through National Institutes of Health grants HL58144 and HD72650.

Correspondence: ² Chandra Yallampalli, Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd., MRB, 11.138, Rt. 1062, Galveston, TX 77555-1062. FAX: 409 747 0475; e-mail: chyallam{at}utmb.edu

This article has been cited by other articles:

				H.W.F. van Eijndhoven, R. Aardenburg, M.E.A. Spaanderman, J.G.R. De Mey, and L.L.H. Peeters Pregnancy Enhances the Prejunctional Vasodilator Response to Adrenomedullin in Selective Regions of the Arterial Bed of Wistar Rats Reproductive Sciences, December 1, 2007; 14(8): 771 - 779. [Abstract] [PDF]