Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy

Citation
Sz. Kim et al., Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy, AM J P-HEAR, 277(6), 1999, pp. H2280-H2289
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
0363-6135 → ACNP
Volume
277
Issue
6
Year of publication
1999
Pages
H2280 - H2289
Database
ISI
SICI code
0363-6135(199912)277:6<H2280:MOENPR>2.0.ZU;2-2
Abstract
Natriuretic peptide (NP) receptors (NPRs) located at the endocardial endoth elium are suggested to be involved in regulating myocardial contractility. However, the characteristics and modulation of NPRs in relation to cardiac failure are not well defined. This study examined the properties of NPRs in ventricular endocardium using quantitative receptor autoradiography, RT-PC R, Southern blot analysis, and activation of particulate guanylyl cyclase ( GC) by NPs. In control rats, specific I-125-labeled rat atrial NP (rANP)(1- 28) binding sites were localized in right (RV) and left ventricular (LV) en docardium. Binding affinities of I-125-rANP(1-28) were remarkably higher in RV than LV endocardium. Radioligand binding at these sites was mostly inhi bited by des [Gln(18),Ser(19),Gly(20),Leu(21),Gly(22)] ANP(4-23), a specifi c NP clearance receptor ligand. mRNAs for all three recognized NPRs were de tected in endocardial cells by RT-PCR and confirmed by Southern blot analys is. Production of cGMP by particulate GC in endocardial cell membranes was stimulated by NPs with a rank order of potency of C-type NP(1-22) much grea ter than brain NP (BNP)(1-26) > ANP(1-28). We also examined the modulation of these NPRs during cardiac hypertrophy induced by monocrotaline (MCT). In MCT-treated rats with pulmonary hypertension, specific I-125-rANP(1-28) bi nding to hypertrophied RV endocardium almost disappeared and cGMP productio n by NPs was significantly decreased. In rats with pulmonary hypertension, plasma levels of ANP and BNP were increased by fivefold compared with contr ols. The results indicate that there is a differential distribution of NPRs in the cardiac chambers, with the most abundant binding sites in RV endoca rdium, that NPR-B is the predominant GC-coupled NPR in ventricular endocard ium, and that endocardial NPRs are downregulated with ventricular hypertrop hy. Downregulation of NPRs may be associated with an increment of endogenou s NP production caused by mechanical overload in hypertrophied ventricle.