Hypertrophy in the denervated heart: A comparison of central sympatholytic treatment with 6-hydroxydopamine and peripheral sympathectomy with nerve growth factor antiserum

Abstract

The effects of widespread destruction of central catecholaminergic structures on systemic hemodynamics, ventricular performance, myocardial hypertrophy and the renin-angiotensin system in developing male spontaneously hypertensive rats of the Okamoto strain (SHR) and control normotensive Kyoto Wistar (WKY) rats were examined and contrasted with the effects of peripheral sympathectomy. Both centrally administered 6-hydroxydopamine (6-OHDA) and nerve growth factor antiserum (NGFAS) prevented the development of hypertension in the spontaneously hypertensive rats but did not affect blood pressure in the control rats. Peripheral vascular resistance remained elevated and cardiac and stroke indexes depressed in both 6-OHDA- and NGFAS-treated spontaneously hypertensive rats despite preservation of normal blood pressure. Ventricular performance was depressed in the sham-treated spontaneously hypertensive rats and was not improved by either treatment. Neither 6-OHDA nor NGFAS treatment prevented the development of left ventricular hypertrophy in the spontaneously hypertensive rats despite the decrease in blood pressure. Plasma renin activity was elevated in the 6-OHDA-treated spontaneously hypertensive rats compared with the sham-treated spontaneously hypertensive control rats but was unaffected by treatment with NGFAS. The data indicate that destruction of central and peripheral noradrenergic structures in the immature spontaneously hypertensive rats prevents the development of hypertension by different physiologic mechanisms but does not alter the suppressed ventricular function, the increased peripheral resistance or the development of myocardial hypertrophy. These results support the concept that increased sympathetic activity is necessary for the development of hypertension in spontaneously hypertensive rats but not for the development of myocardial dysfunction or hypertrophy.