Despite irrefutable evidence concerning the importance of sympathetic nerves in cardiovascular homeostasis, it has not been shown that sympathetic dysfunction alone can cause hypertension. This proposal will test the hypothesis that hypertension results only when sympathetic overactivity is superimposed on other predisposing factors. Whenever technically feasible, experiments will be done on conscious rats to avoid distortion of results by anesthesia. Aside from blood pressure and heart rate, sympathetic nerve activity will also be recorded. Sympathetic vasomotor tone will be increased by chronic electrical stimulation of the hypothalamus or by prolonged exposure to mechanical agitation (vibration) and these procedures will then be combined with changes in salt intake or in renal, adrenocortical, or buffer nerve function. Since our previous studies indicate that sympathetic hyperactivity emanting from the posterior hypothalamus contributes to initiate and to maintain pressure elevations in spontaneously hypertensive rats, the responsible mechanisms will be examined further. Young rats will be treated chronically with propranolol and if subsequent development of spontaneous hypertension is inhibited, pressor and neural responses to hypothalamic stimulation will be measured to determine if sympathetic activity has been diminished centrally. Hyperactive centers in the hypothalamus will be identified by recording cardiovascular and neural effects of stimulating suspected sites following destruction of other hypothalamic areas. Similar involvement of other parts of the brain particularly the septum and amygdala will be explored, first in normotensive, and then in hypertensive rats. By providing much needed information on basic derangements in experimental hypertension the proposed studies could improve our understanding of the disease and facilitate development of unempirical and effective therapy.
NIH ExPorter
NIH ExPorter