Abstract 12331: Activation of Mineralocorticoid Receptors in the Rostral Ventrolateral Medulla Enhances Sympathetic Activity in Stroke-Prone Spontaneously Hypertensive Rats
Background: Mineralocorticoid receptor (MR) antagonists have been shown to benefit patients with heart failure by probably preventing the end-organ damage. It has also been reported that MR regulates sodium transport and maintain extracellular fluid volume and blood pressure via epithelial Na channels. In addition, it has been reported plasma or locally produced aldosterone can bind MR in the brain and causes sympathoexcitation and hypertension. We examined if activation of the MR pathway in the rostral ventrolateral medulla (RVLM, the cardiovascular center) contributes to neural mechanism of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP).
Methods and Results: In anesthetized Wistar-Kyoto (WKY) rats and age-matched SHRSP, we microinjected aldosterone, Na-rich artificial cerebrospinal fluid (aCSF) or eplerenone into the RVLM. Microinjection of aldosterone or Na-rich aCSF increased arterial pressure (AP) and renal sympathetic nerve activity (RSNA) dose-dependently. The increases in AP and RSNA were significantly greater in SHRSP than in WKY. Microinjection of eplerenone decreased AP and RSNA in both strains and the decreases in those variables were significantly greater in SHRSP than in WKY (ΔMAP -33.6 ± 3.2, n=5 vs. -13.1 ± 2.3 mmHg n=5; p<0.05, ΔRSNA -11.3 ± 2.1, n=3 vs. -4.4± 0.6% n=4, p<0.05). In SHRSP and WKY, the prior injection of MR antagonist prevented the aldosterone induced pressor response, whereas partially prevented the Na-rich aCSF induced pressor response. The protein expression levels of MR in the RVLM did not differ between the 2 strains. However, glucocorticoid-regulated kinase (sgk1), which is induced by MR and indicated activity of MR, were significantly greater in SHRSP than WKY.
Conclusion: These findings indicate that activation of MR in the RVLM enhances sympathetic activity thereby contributing to the neural mechanism of hypertension.
- © 2011 by American Heart Association, Inc.