Central blockade of aldosterone synthase (AS) and lesion of the subfornical organ (SFO) attenuate subcutaneous (sc) aldosterone‐induced hypertension

Abstract

Central blockade of mineralocorticoid receptors (MR) prevents sc aldosterone (aldo) induced hypertension. We examined whether the SFO and aldo synthesized locally in the brain mediate sc aldo - induced hypertension. Wistar rats with telemetry probes were treated with icv infusion of AS inhibitor FAD286 (25 μg/d); icv eplerenone (5 μg/d); or icv vehicle. After 2 d, sc infusion of aldo (1 μg/h) was started and 0.9% saline given as drinking water for all. One extra group of rats was given saline without sc aldo. In a 2nd set of rats with telemetry, electrolytic lesions/sham lesions of the SFO were performed and sc aldo and saline started 1 wk after. Three wk after sc aldo, rats were decapitated and brain and trunk blood collected. Inhibition of AS, MR blockade, and SFO lesions attenuated sc aldo -induced pressor responses by ~60%. These results suggest that the SFO plays a crucial role in sc aldo induced hypertension possibly by responding to circulating aldo and relaying signals to increase local production of aldo and activate aldo-MR neuromodulatory pathways. Data=means± SE (n=5–9/group). *p<0.05, vs. others, a:p<0.05, vs. vehicle or sham lesion. (Supported by grant # FRN:MOP-74432 from the Canadian Institutes of Health Research)