Akademik Veri Yönetim Sistemi
FASEB Journal, cilt.11, sa.3, 1997 (SCI-Expanded)
The present study was undertaken to investigate the effects of human adrenomedullin13-52 (hADM13-52) in the rat pulmonary vascular bed in vivo. Since pulmonary blood flow and left atrial pressure were held constant, changes in pulmonary arterial pressure directly reflected changes in pulmonary vascular resistance. Results of the present study demonstrate the pulmonary vasodilator response to hADM13-52 in the intact rat, and the pulmonary vasorelaxant response to hADM13-52 in rat PA rings was inhibited by L-NAME (L-NG-nitro-L-arginine methyl ester), L-NIO (L-N5-(1-iminoethyl) omithine HCL), methylene blue, endothelium removal, hADM26-52, and iberiotoxin (IbTx), whereas meclofenamate, calcitonin gene-related peptide8-37 (CGRP8-37), glybenclamide and apamin were without effect. The present data suggest ADM acts on a functional and specific peptide receptor population in the pulmonary vascular bed that is coupled to endothelial-derived nitric oxide release. This nitric oxide release leads to cGMP-dependent K+ channel activation, which produces a pulmonary vasorelaxant response through hyperpolarization of pulmonary vascular smooth muscle cells. Since ADM is synthesized by the lung and endothelial cells, the present data suggest ADM may act as an ionic vasodilator substance to regulate the pulmonary vascular bed in an autocrine and paracrine manner.