Published online before print September 18, 2006, doi: 10.1161/01.HYP.0000241432.82676.4f
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(Hypertension. 2006;48:822.)
© 2006 American Heart Association, Inc.
Editorial Commentaries |
Is There a New Treatment for Hypertensive Disease in the Horizon?
Role of Soluble Guanylate Cyclase
From the Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, University of Alabama in Birmingham, Birmingham, Ala.
Correspondence to Veronica Franco, Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, University of Alabama at Birmingham, ZRB 1024, 703 19th St South, Birmingham, AL 35294. E-mail vfranco@uab.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Left ventricular hypertrophy (LVH) and fibrosis have received special attention as possible therapeutic targets in preventing cardiovascular complications of hypertension. Suppression of neurohormonal factors that predispose to target organ damage, in addition to blood pressure (BP) reduction, seems to be of importance in modulating cardiac remodeling and fibrosis in hypertensive heart disease. In the normal heart, the effects of endogenous hypertrophic/profibrotic factors, including angiotensin II (Ang II), aldosterone, and inflammatory cytokines, such as transforming growth factor-ß, growth factors, and catecholamines, are balanced by the action of growth-inhibiting/antifibrotic factors, including NO, natriuretic peptides, and bradykinin.
Previous studies have shown that atrial natriuretic peptide (ANP) modulates cardiac hypertrophy and fibrosis in response to a variety of hemodynamic stresses.1–3 In the setting of hypertension or in the absence of the counterregulatory effects of ANP signaling, as in the ANP null (Nppa–/–) or heterozygous (Nppa+/–) mouse or the mouse lacking natriuretic peptide type A receptors (Npr–/–), the unopposed profibrotic/hypertrophic factors predominate, and LVH with interstitial and perivascular fibrosis develops. In vitro studies have demonstrated that ANP inhibits cardiac fibroblast proliferation, myofibroblast transformation, and expression of extracellular matrix, including collagen, via a signaling pathway that involves particulate guanylate cyclase, cGMP, and protein kinase G.4 This cardioprotective signaling cascade has attracted the interest of clinicians because of the recent demonstration that the phosphodiesterase 5 inhibitor sildenafil (Viagra) reverses cardiac hypertrophy and remodeling in mice subjected to pressure overload stress.5 Unfortunately, no orally active analog of ANP or other stimuli of
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