Dewan S. A. Majid
Tulane University School of Medicine, USA
Title: The pathophysiological roles of peroxynitrite in salt-sensitive hypertension
Biography
Biography: Dewan S. A. Majid
Abstract
Normally, superoxide (O2-) remains at minimal levels in tissues as it reacts with nitric oxide (NO) to form peroxynitrite (ONOOˉ). Although studies have demonstrated a reciprocal regulation of renal tubular sodium (Na+) reabsorption by NO and O2-, the specific role for ONOOˉ in the regulation of renal sodium excretion is not yet clearly defined. It has been demonstrated that an interaction between NO and O2- forming ONOOˉ plays an important reno-protective role in the kidney which helps to prevent excessive tubular Na+ reabsorption in conditions such as in elevated renin-angiotensin system. However, its regulation in various pathophysiological conditions, particularly in salt-sensitive hypertension is not yet clarified. The ONOOˉ formation is increased by angiotensin II (AngII) as well as by high salt (HS) intake as both of these stimulate both NO and O2- production. However, conditions such as impairment in NOS activity, its pharmacological inhibition or gene deletion, reduces the formation of ONOOˉ. Recent findings that chronic AngII with HS intake results in aggravated hypertension and renal injury in endothelial NO synthase knockout mice (a model for minimal ONOOˉ formation) compared to those in wild-type mice that suggest a protective role for ONOOˉ in these adverse effects of AngII. This talk will present evidence from different studies in our laboratory and others implicating the functional roles of ONOOˉ in a coordinated regulation of kidney function, an imbalance of which could be involved in the pathophysiology of salt-sensitive hypertension.