Modulated vasodilator responses to natriuretic peptides in rats exposed to chronic hypoxia.
Natriuretic peptides (NPs), such as atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and adrenomedullin (ADM), are endogenous vasodilators acting via specific receptors. This study addressed the question of how pulmonary artery (PA) responses to these peptides and the gene expression 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 was compared with messenger ribonucleic acid (mRNA) levels of NP-A and -B receptors, which bind to ANP and CNP, respectively, as determined by ribonuclease (RNase) protection assay. Chronic hypoxia increased the maximal relaxation elicited by ANP, but the responses to CNP and 8-bromo-cGMP were unchanged. Chronic hypoxia did not change NP-A and -B receptor mRNA levels. The results showed that pulmonary artery response to atrial natriuretic peptide is selectively enhanced, possibly via a post-transcriptional modulation of its receptor in chronically hypoxia rats. These pharmacological characteristics of atrial natriuretic peptide are consistent with the hypothesis that the atrial natriuretic peptide system is protective against the progression of pulmonary hypertension.
Mitani
Y
Y
Dept of Paediatrics, Mie University School of Medicine, Tsu, Japan.
Maruyama
J
J
Yokochi
A
A
Maruyama
K
K
Yoshimoto
T
T
Naruse
M
M
Sakurai
M
M
D053607:Adrenomedullin; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D010455:Peptides; D014665:Vasodilator Agents; D020098:Natriuretic Peptide, C-Type; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D015740:Calcitonin Gene-Related Peptide