Published online before print November 5, 2007, doi: 10.1161/HYPERTENSIONAHA.107.100032
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2007;50:1009.)
© 2007 American Heart Association, Inc.
Editorial Commentaries |
LA419, a Novel Nitric Oxide Donor, Prevents Cardiac Remodeling Via the Endothelial Nitric Oxide Synthase Pathway
NO Donors as a Means of Antiremodeling
From the Department of Pathophysiology (L.P., F.S.), School of Medicine, Comenius University, Bratislava, Slovak Republic; Institute of Normal and Pathological Physiology (L.P.), Slovak Academy of Sciences, Bratislava, Slovak Republic; and the 3rd Clinic of Medicine (F.S.), School of Medicine, Comenius University, Bratislava, Slovak Republic.
Correspondence to Ludovit Paulis, Institute of Pathophysiology, School of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovak Republic. E-mail ludo@lfuk.sk
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The discovery of NO as the endothelium-derived relaxing factor unleashed new horizons. NO is a ubiquitous radical exerting both hemodynamic and tissue growth–modifying effects. The vasodilative and antiproliferative properties of NO produced by endothelial NO synthase are considered to act beneficially within the cardiovascular system. However, under certain circumstances, the inducible NO synthase produces large quantities of NO that may be harmful.1 Most NO effects can be attributed to the activation of soluble guanylate cyclase and the subsequent cascade of events including enhanced cGMP concentration, activation of cGMP-dependent kinase-1, and reduced intracellular calcium levels in target cells. NO acts as a principal regulator of vascular function. Venodilatation and arterial relaxation result in a decrease of left ventricular pressure and chamber size, leading to attenuation of oxygen consumption. NO dilates epicardial coronary arteries, enhances collateral flow, and inhibits platelet aggregation. Moreover, NO was shown to inhibit collagen synthesis and to reduce cardiomyocyte growth. NO, thus, represents an opposing force to vasoconstrictors and growth-promoting substances, such as angiotensin II and endothelin.
The depression of NO signaling, including downregulated expression and attenuated enzymatic activity of NO synthase and scavenging of NO by oxygen-derived free radicals, seems to be a principal disorder in endothelial dysfunction. NO deficiency is, therefore, related to many cardiovascular pathologies, such as coronary atherosclerosis with myocardial ischemia, arterial hypertension with left ventricular hypertrophy, or heart failure. It is obvious that NO plays an important role in the circulatory physiology.
Nevertheless, the impact of therapeutically increased NO bioactivity on cardiovascular morbidity
Related Article:
Hypertension 2007 50: 1049-1056.