SYMPATHOADRENAL SYSTEM IS CRITICAL FOR STRUCTURAL-CHANGES IN GENETIC-HYPERTENSION

In spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, we examined tissue and adrenal norepinephrine concentrations, left ventricular (LV) weight, LV weight/body weight ratio (LV/BW), hindquarter resistance properties, ie, perfusion pressures at maximum dilatation and constriction (PP(max), PP(min)), and the slope of the methoxamine log dose-PP curve. In series 1, we studied 4-week-old controls (SHR(c), WKY(c)), sympathectomized rats (SX; SHR(sx), WKY(sx)), and SX rats also given prazosin (SXP; SHR(sxp), WKY(sxp)). With SX and SXP, adrenal norepinephrine concentrations increased in both strains, but tissue (LV, muscle, kidney) norepinephrine was depleted. At 4 weeks, LV/BW, PP(min), and PP(max), were all greater in SHR(c) than in WKY(c). With SX, these differences between strains remained unchanged, but SXP abolished them completely, indicating the importance of blockade of a-adrenergic receptor stimuli of adrenal origin. In SHR(c) (but not in WKY(c)), there was evidence of reinnervation after 4 weeks of SX. Hence, in series 2, the SXP period was extended to 8 weeks, and we studied SHR(c), WKY(c), SHR(sxp), and WKY(sxp). Systolic blood pressure was already elevated at 4 weeks in SHR(c), and by 35 weeks it was 64 mm Hg greater than in WKY(c). At 21 and 35 weeks, IN/BW, PP(max) PP(min), and slopes were all greater in SHR(c) than in WKY(c) and the findings suggested greater LV and vascular hypertrophy than at 4 weeks. In SHR(sxp) hypertension, LV hypertrophy and the vascular changes were completely prevented over the entire 35-week observation period. SXP mainly affected SHR and had few effects on WKY rats. The sympathetic nerves and adrenals are probably the sources of alpha-adrenergic receptor stimulation in young SHR. They account for the development of hypertension and for most of the cardiovascular structural differences between SHR and WKY rats.