Effects of esaxerenone on blood pressure and sodium balance in Dahl salt-sensitive hypertensive rats

Abstract

The nonsteroidal mineralocorticoid receptor blocker, esaxerenone, is effective in reducing blood pressure (BP) in hypertensive patients. However, the mechanism responsible for anti-hypertensive effect of esaxerenone is not clear. Therefore, we investigated esaxerenone-driven sodium homeostasis and its association with changes in BP in Dahl salt-sensitive (DSS) hypertensive rats. BP was measured by a radiotelemetry system, and sodium homeostasis was determined by an approach of sodium intake (food intake) and excretion (urinary excretion) in DSS rats with a lowsalt diet (0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD plus 0.001% esaxerenone (w/w), and HSD plus 0.05% furosemide. HSD-fed DSS rats showed a dramatic increase in BP with a non-dipper pattern, while esaxerenone treatment, but not furosemide, significantly reduced BP with a dipper pattern. The cumulative sodium excretion in the active period was significantly elevated in esaxerenone-and furosemide-treated rats compared with their HSD-fed counterparts. However, a significant increase in the sodium/potassium ratio was only observed in esaxerenone-treated rats. Sodium content in the skin, skinned carcass, and total body tended to be lower in esaxerenone-treated rats than in their HSD-fed counterparts, while these values were unchanged in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. These data indicate that esaxerenone-induced reduction in BP is associated with improvement of body sodium homeostasis in salt-dependent hypertension.