ADRENOMEDULLIN ACTIVITY IN CHRONICALLY HYPOXIC RAT LUNGS

Adrenomedullin (AM) is a novel vasodilator with structural similaritie s to calcitonin gene-related peptide (CGRP). This study investigated A M activity in the rat lung during hypoxia-induced pulmonary hypertensi on. Both rat AM (0.2-10 nmol) and alpha-CGRP (0.2-2 nmol) produced dos e-related reductions in pulmonary artery pressure in the isolated perf used lung ventilated with 2% O-2. Pretreatment with alpha-CGRP, which demonstrated tachyphylaxis, or its antagonist, CGRP-(8-37), reduced th e hypotensive response to AM, suggesting that part of the response to AM is mediated by CGRP receptors. I-125-labeled AM and I-125-labeled C GRP binding was significantly increased in lung membranes from 7-day h ypoxic animals (AM from 1.94 +/- 0.3 to 3.36 +/- 0.4 and CGRP from 0.0 6 +/- 0.01 to 0.12 +/- 0.02 pmol/mg protein), with no change in dissoc iation constant. Moreover, the hypotensive response to both peptides w as increased in the lungs of 7-day hypoxic rats. There was no signific ant change in lung immunoreactive AM concentrations (hypoxic 5.04 +/- 0.48 vs. control 6.28 +/- 0.76 pmol/g wet wt of tissue) or steady-stat e AM mRNA levels in 7-day hypoxic rats. Nonetheless, AM may be useful for the acute pharmacological manipulation of pulmonary artery pressur e in hypoxia-induced pulmonary hypertension.