Abstract
P66 Earlier studies have demonstrated evidence for increased reactive oxygen species (ROS) and enhanced nitric oxide synthase (NOS) expression and NO production in spontaneously hypertensive rats (SHR). Given the negative feedback regulation of NOS by NO, we hypothesized that enhanced NO inactivation by ROS may contribute to compensatory upregulation of NOS in SHR. The present study was designed to test this hypothesis. Eight-week old male SHR were treated for three weeks with either a placebo or the potent antioxidant, lazaroid (des-methyltirilazad, 10 mg/kg/day by gastric gavage). A group of age-matched male Wistar Kyoto (WKY) rats served as controls. Tail arterial blood pressure and urinary excretion of NO metabolites (i.e. nitrate and nitrite, NO x ) were measured. In addition, immunodetectable NOS isotype proteins in the vascular, renal, cardiac and cerebral tissues were measured by Western blot. Compared to the WKY group, the placebo-treated SHR group showed a marked elevation of blood pressure (129±6 vs 198±8 mmHg, P
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