Modulated vasodilator responses to natriuretic peptides in rats exposed tochronic hypoxia

Natriuretic peptides (NPs), such as atrial natriuretic peptide (ANP), C-typ e natriuretic peptide (CNP), and adrenomedullin (ADM), are endogenous vasod ilators acting via specific receptors, This study addressed the question of hen. pulmonary artery (PA) responses to these peptides and the gene expres sion of their receptors are modulated in pulmonary hypertension rat models exposed to chronic hypoxia. In this study, isometric tension was measured in PA rings exposed to these NPs and 8-bromoguanosine 3', 5' - cyclic monophosphate (8-bromo-cGMP). It w as compared with messenger ribonucleic acid (mRNA) levels of NP-A and -B re ceptors, which bind to ANP and CNP, respectively, as determined by ribonucl ease (RNase) protection assay. Chronic hypoxia increased the maximal relaxation elicited by ANP, but the r esponses to CNP and 8-bromo-cGMP were unchanged. Chronic hypoxia did not ch ange NP-A and -B receptor mRNA levels. The results showed that pulmonary artery response to atrial natriuretic pep tide is selectively enhanced, possibly via a post-transcriptional modulatio n of its receptor in chronically hypoxia rats. These pharmacological charac teristics of atrial natriuretic peptide are consistent with the hypothesis that the atrial natriuretic peptide system is protective against the progre ssion of pulmonary hypertension.