OXYGEN RADICAL SCAVENGERS AND RENAL PROTECTION BY INDAPAMIDE DIURETICIN SALT-INDUCED HYPERTENSION OF DAHL STRAIN RATS

In addition to the hemodynamic components, the roles of various humora l factors have been emphasized in the progression of vascular and rena l injury in hypertension. Radical scavenging properties have attracted much attention in this field. This article discusses the implication of antioxidant properties of the antihypertensive diuretic indapamide on renal injury in Dahl salt-sensitive (Dahl S) rats. Hydroxyl radical s, oxygen radicals toxic to cellular membranes, are eradicated by inda pamide in different assay systems, e.g., reduction of alpha-alpha-diph enyl-beta-picrylhydrazyl, rat brain homogenate, or xanthine-xanthine o xidase systems. Such antioxidant effects of indapamide are primarily d ue to inhibition of lipid peroxidation induced by hydroxyl radicals, a nd this mechanism may stimulate prostacyclin generation through activa tion of prostacyclin synthase. In fact, the antioxidant properties of indapamide are well expressed in vivo as well; indapamide treatment re duced oxygen radicals in the kidney of Dahl S rats with hypertension. This was accompanied by a functional improvement of the kidney; decrea ses in urinary protein and n-acetylglucosaminidase excretion and an in crease in glomular filtration rate were observed. In addition, indapam ide morphologically ameliorated the renal injury, and decreased glomer ular sclerosis score, arterial injury, and renal tubular injury. Trich loromethiazide reduces blood pressure similar to that produced by inda pamide. However, trichloromethiazide did not lead to reduction of oxyg en radicals in the kidney, and did not improve the functional disturba nce or morphological injury seen in Dahl S rats. These results indicat e that indapamide has antioxidant properties, and in addition to blood pressure reduction, such radical scavenging effects may contribute to its beneficial effects on renal function in vivo.