Aldosterone induces sympatho‐excitation via brain mitogen‐activated protein kinase signaling pathways in rat

Abstract

Recent evidence shows that brain mitogen‐activated protein kinase (MAPK) signaling plays a critical role in mediating renin‐angiotensin system influences on sympathetic drive. We tested the contribution of brain MAPK to aldosterone‐induced sympatho‐excitatory responses. In anesthetized rats, we recorded renal sympathetic nerve activity (RSNA), mean blood pressure (MBP) and heart rate (HR) at baseline and for 4 hours during intravenous (IV) infusion of aldosterone, with or without concomitant intracerebroventricular (ICV) infusion of the mineralocorticoid (MR) antagonist RU28318 or selective MAPK inhibitors. Hypothalamic tissues were then collected for molecular analysis. Aldosterone infusion increased (p<0.05) RSNA, HR and MBP, as well as the hypothalamic expression of phosphorylated (relative to total) p44/42 and p38 MAPK. Concomitant ICV infusion of RU28318 blocked phosphorylation of p44/42 MAPK, blunted phosphorylation of p38 MAPK, and prevented the increases in RSNA, HR and MBP. The p44/42 MAPK inhibitor PD98059 reduced the aldosterone‐induced RSNA, HR and MBP responses, and the p38 MAPK inhibitor SB203580 reduced the aldosterone‐induced HR and MBP responses. These data suggest that aldosterone, originating in the periphery and acting on brain MR, activates brain MAPK pathways to produce sympatho‐excitatory responses. Supported by a VA Merit Review Award.