ADRENOMEDULLIN MEDIATED NITRIC OXIDE RELEASE IN THE REGULATION PLACENTAL ARTERIAL VASCULAR TONE. • 451

Abstract

The role of agonist and constitutive nitric oxide (NO) release in the regulation of human placental vascular tone are not known. ADM is a recently discovered hypotensive peptide isolated from pheochromocytoma cells that shares structural homology to Calcitonin Gene Related Peptide, (CGRP). Adrenomedullin has been shown to produce vascular relaxation through NO and cyclic AMP mediated intracellular signal pathways. We investigated in vitro responses to both peptides in cannulated chorionic plate arteries (CPA) from term uncomplicated pregnancies. Vessels were cannulated on micropipettes under constant intraluminal pressure and changes in diameter (<400 microns) were measured through a videodimension analyzer. Percent relaxation in response to 0.1uM synthetic human ADM and CGRP were observed following submaximal preconstriction with U46619. Vessels were rechallenged with either peptide following equilibration with 0.1mM of the NO synthase inhibitor L-NNA. An additional group was studied following removal of the endothelium (EC-) by perfusing the lumen with lcc air at atmospheric pressure. Results shown below are Mean ± SEM (n=6) percent increase lumen diameter (*, p<0.05 vs. control). Membrane receptors and intracellular signal pathways to both peptides are present in term CPA. The in vitro response to ADM is mediated by endothelial NO release. Selective inhibition of the response to ADM but not CGRP by L-NNA strongly suggests two distinct receptor populations. Constitutive NO release may play an important role in the regulation of placental vascular tone in vivo. Table