Involvement of brain mineralocorticoid receptor in salt-enhanced hypertension in spontaneously hypertensive rats

We recently showed that brain mineralocorticoid receptors (MRs) are involve d in blood pressure and kidney function control in normotensive Wistar rats . We now assessed the involvement of brain MRs in spontaneously hypertensiv e rats (SHR), in which the presence of adrenocorticoids has been shown to b e required for the development of hypertension. The effect of a single intr acerebroventricular (ICV) injection of an MR antagonist (RU28318) on systol ic blood pressure (SBP) and renal function was examined in conscious adult SHR and Wistar-Kyoto rats (WKY) maintained on a standard-sodium diet (0.4% Na+). In WKY, a long-lasting decrease in SBP was caused by the ICV injectio n of 10 ng RU28318 as previously reported in Wistar rats, associated with i ncreased urinary excretion of water and electrolytes. In SHR maintained on the standard diet, the ICV injection of RU28318 (10 or 100 ng) had no effec t on cardiovascular and renal functions. However, the ICV injection of 10 n g RU28318 in SHR after 3 weeks of high sodium intake (8% Na+) caused a long -lasting decrease in SBP. The effect was present at 8 hours (Delta SBP 34+/ -2 mm Hg), persisted at 24 hours (Delta SBP 29 +/- 1 mm, Hg), and disappear ed at 48 hours after the injection. The hypotension was not associated with changes in heart rate, urinary excretion of water and electrolytes, and pl asma renin activity, whereas renal denervation did not affect the decrease in SBP. A more pronounced decrease in SBP (49 +/- 3 mm Hg at 8 hours) was o bserved with 100 ng RU28318. This dose of the antagonist was without effect after subcutaneous administration. Thus, brain MRs appear to participate i n the maintenance of hypertension in conscious adult SHR sensitized by sodi um loading.