Age-Dependent Salt-Induced Hypertension in the Rat: Prevention with DSP-4, A Selective Noradrenergic Neurotoxin

Abstract

The present study was performed to determine if chronic administration of a high salt diet induces hypertension similarly in young and adult rats and if treatment with DSP-4 alters the development of the hypertension. Three- (young) and ten- (adult) week-old male Sprague-Dawley rats were fed either a standard rat chow diet (0.71% NaCl), a 4% NaCl diet or an 8% NaCl diet for 12 weeks. Systolic blood pressure, using a standard tail-cuff technique, and body weight were recorded weekly during the dietary treatment period. Direct mean arterial pressure, heart rate, heart weight and kidney weight were determined after 12 weeks. Body weight was slightly reduced in young rats on the 8% NaCl diet. A significant increase in blood pressure as well as heart weight was observed only in young rats on the 8% NaCl diet. An increase in kidney weight was observed in both young and adult rats on the 8% NaCl diet. DSP-4 treatment prevented the development of hypertension as well as cardiac hypertrophy in rats fed the high salt diet but had no effect on rats receiving the normal diet. Body and kidney weights were similar in vehicle- and DSP-4-treated rats on the 8% NaCl diet. These results demonstrate that a critical developmental/maturational period exists during which the young rat is susceptible to the hypertensinogenic effects of a high salt diet. An intact central noradrenergic system appears to be necessary for the expression of this enhanced susceptibility and the subsequent development of hypertension.