The Anterior Hypothalamus and Salt-Sensitive Hypertension

Abstract

Early studies in our laboratory suggested that in young (3–12 weeks of age) male spontaneously hypertensive rats (SHR), ingestion of a high NaCl diet exacerbates hypertension (Fig. 1), increases peripheral sympathetic nervous system activity and alters the norepinephrine (NE) content of a hypothalamic nucleus known to be involved blood pressure (BP) regulation (Winternitz et al, 1982a, b; Wyss et al., 1987). Exposure to a high (8% compared to 0.6%) NaCl diet for 2 weeks causes increases in both arterial pressure and peripheral sympathetic nervous system activity and a decrease in NE stores in anterior hypothalamic area but not in other brain regions tested in these animals. None of these NaCl-induced alterations occur in NaCl resistant normotensive WistarKyoto (WKY) rats or NaCl resistant SHR (Wyss et al, 1997). Subsequent studies demonstrated that exposure to a high NaCl diet selectively reduces the turnover of NE in the anterior hypothalamic nucleus (AHN), but not in other hypothalamic nuclei of young, NaCl sensitive male SHR (Chen et al., 1988). These findings are consistent with the hypothesis that dietary NaC1 supplementation exacerbates hypertension in SHR by decreasing the release of NE from nerve terminals in the AHN, thus reducing the activity of the AHN neurons and decreasing the inhibition of peripheral sympathetic nervous system activity (166-1). NaCl-resistant SHR (SHR-R) and WKY have a genetically based resistance to these effects of dietary NaCl and as a result do not display these responses to a high NaCl diet (Wyss et al., 1997). The pushpull microperfusion technique was then used to provide direct evidence of selective reduction in NE release from nerve terminals in the AHN of NaCl supplemented SHR (Chen et al., 1991) (Fig. 3). Dietary NaCl had no effect on NE release in other brain regions tested in SHR and no effect on NE release in the AHN of NaCl-resistant WKY. Subsequent studies focused on defining the functional significance of the selective NaCl-induced reduction in NE release in the AHN of SHR and identifying the local and systemic mechanisms responsible.