Central AT1R stimulation increases hypothalamic aldosterone: further evidence for a pivotal role of hypothalamic aldosterone in Ang II induced hypertension

Chronic increase in circulating Ang II by subcutaneous (sc) infusion of Ang II increases hypothalamic aldosterone thereby activating an aldosterone‐“ouabain” neuromodulatory pathway which contributes to sustained activation of the PVN, and progressive sympathetic hyperactivity and hypertension (Huang et al. Am J Physiol 299:H422, 2010). The present study examined whether icv infusion of Ang II at doses which are ineffective when administered peripherally also increases hypothalamic aldosterone and cause hypertension. Ang II at 2.5 or 12.5ng/min or artificial CSF (vehicle) was infused icv via minipumps in Wistar rats for 14 days. On day 14, BP and HR were recorded in conscious rats, and changes in aldosterone and corticosterone levels in the hypothalamus and hippocampus were measured by radio‐immuno assays. Sc infusion of Ang II at the same rates had no effects on BP, HR and hypothalamic aldosterone level.Vehicle Ang II 2.5ng/min Ang II 12.5ng/minH 2 O intake, ml/d 34±5 289±52 * 286±36 * MAP, mmHg 103±4 122±4 * 150±7 * † HR, bpm 392±22 439±22 453±18 * Hypothalamus Aldo, pg/g 327±67 1229±88 * 1413±524 * Cort, ng/g 33±6 225±51 * 255±44 * Hippocampus Aldo, pg/g 404±162 1370±178 * 1515±437 * Cort, ng/g 26±5 159±37 * 146±20 *Data are mean±SE. * p<0.05, vs vehicle. † p<0.05, vs Ang II at 2.5ng/min.The present study further supports the concept that central AT 1 receptor stimulation increases local production of aldosterone in the hypothalamus, which may contribute to Ang II‐induced sympathetic hyperactivity and hypertension. (Supported by grant #FRN:MOP‐74432 from Canadian Inst of Health Research)