CENTRAL CONTROL OF SYMPATHETIC FUNCTION

流行病学研究表明，遗传易感性和

Epidemiological studies have suggested that both genetic predisposition and the amount of sodium consumed in the diet contribute significantly to the prevalence of human hypertension. The proposed experiments will study an animal model where genetic factors and dietary sodium are important for the development of hypertension. The Dahl model of genetic salt-induced hypertension utilizes a unique inbred strain of rats that have normal blood pressure when fed a low sodium diet, but develop hypertension when fed a high sodium diet. Recent work from this laboratory has demonstrated that abnormalities in neural circulatory control contributes importantly to the development of hypertension in the Dahl strain. Dahl salt-sensitive rats have impaired arterial baroreflexes prior to and during the development of hypertension and facilitated peripheral sympathetic function contributes significantly to elevated arterial pressure and increased vascular resistance in this model of hypertension. There is also suggestive evidence for central nervous system abnormalities in Dahl salt-sensitive rats. I propose to utilize my training in central nervous system mechanisms in conjunction with my recent experience investigating peripheral neural mechanisms in the Dahl strain to conduct studies into the nature of central nervous system control of peripheral sympathetic function in the Dahl model of salt-induced hypertension. The general goal of the proposed studies is to determine if Dahl salt-sensitive rats exhibit genetic abnormalities in central neural control of sympathetic function in the prehypertensive stage when fed a low sodium diet and whether such abnormalities are accentuated or unmasked by salt feeding and thus contribute to the development of hypertension. This will be accomplished by determining 1) if sympathetic nervous system activity is increased in Dahl hypertension, 2) whether increased central sympathetic drive and/or impaired baroreflex control contribute to increased sympathetic activity, and 3) the level of central vasomotor organization required for generating increased sympathetic activity in Dahl hypertension. In addition, the effect of antihypertensive brain lesions on central sympathetic control mechnism will be examined. The results of these studies will provide knowledge concerning the basic physiological mechanisms underlying the relationship between genetic predisposition, dietary sodium, and the central and peripheral nervous systems in the pathogenesis of salt-induced hypertension.