The therapeutic effect of natriuretic peptides in heart failure; differential regulation of endothelial and inducible nitric oxide synthases.

Abstract:

:The abnormal regulation of nitric oxide synthase activity represents an underlying feature of heart failure. Increased peripheral vascular resistance, and decreased renal function may be in part related to impaired endothelium-dependent nitric oxide (NO) synthesis. Paradoxically, the chronic production of NO by inducible nitric oxide synthase (iNOS) in heart failure exerts deleterious effects on ventricular contractility, and circulatory function. Consequently, pharmacologically improving endothelium-dependent NO synthesis and the concomitant inhibition of iNOS activity would be therapeutically advantageous. Interestingly, natriuretic peptides have been shown to differentially regulate endothelial NOS (eNOS) and iNOS activity. Moreover, in both patients and animal models of heart failure, pharmacologically increasing plasma natriuretic peptide levels ameliorated vascular tone, renal function, and ventricular contractility. Based on these observations, the following review will explore whether the therapeutic benefit of the natriuretic peptide system in heart failure may occur in part via the amelioration of endothelium-dependent NO synthesis, and the concomitant inhibition of cytokine-mediated iNOS expression.

journal_name

Heart Fail Rev

journal_title

Heart failure reviews

authors

Calderone A

doi

10.1023/a:1022147005110

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

55-70

issue

1

eissn

1382-4147

issn

1573-7322

pii

5114467

journal_volume

8

pub_type

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