Hypothalamic microinjection of alpha2-adrenoceptor agonists causes greater sympathoinhibition in spontaneously hypertensive rats on high NaCl diets


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Abstract

We tested the hypothesis that in NaCl-sensitive spontaneously hypertensive rats (SHR-S) maintained on high NaCl diets, sympathoinhibitory neurons in the anterior hypothalamic area display increased responsiveness to α2-adrenergic receptor stimulation, giving rise to exaggerated depressor responses. Clonidine (0.6–2.5 (μg) was microinjected directly into the anterior hypothalamic area of SHR-S maintained for 2 weeks on high (8%) and normal (1%) NaCl diets, and blood pressure and heart rate responses were monitored. Controls were NaCl-resistant SHR (SHR-R) and normotensive Wistar-Kyoto (WKY) rats. Clonidine microinjection into the anterior hypothalamic area resulted in dose-dependent rapid-onset depressor and bradycardic responses that were significantly greater in SHR-S fed on a high NaCl diet. In SHR-R and WKY rats, the high NaCl diet had no significant effect on blood pressure or heart rate responses to clonidine. Further studies demonstrated that the response to microinjection of clonidine into the rat anterior hypothalamic area was location-specific, since injections into surrounding hypothalamic nuclei gave a longer latency in the onset of either depressor and bradycardic responses or pressor and tachycardic responses. The response of clonidine was blocked by concurrent microinjection of the selective α2-adrenergic antagonist rauwolscine but not by the α-adrenergic antagonist prazosin, confirming that the response was α2-adrenoceptor-specific. Microinjection of the selective α2-agonist guanabenz into the anterior hypothalamic area produced depressor and bradycardic responses in SHR-S and Sprague-Dawley rats, while microinjection of the selective α-agonist phenylephrine into the anterior hypothalamic area had no effect on either blood pressure or heart rate. These data are consistent with the hypothesis that sympathoinhibitory neurons in the anterior hypothalamic area of SHR-S fed a high NaCl diet display an increased response to stimulation of the anterior hypothalamic area α2-adrenoceptor, presumably reflecting upregulation of α-adrenoceptors in this area in response to decreased noradrenergic input.

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