PS-BPB03-1: ASSOCIATION OF ANTIHYPERTENSIVE EFFECTS OF ESAXERENONE WITH THE INTERNAL SODIUM BALANCE IN DAHL SALT-SENSITIVE HYPERTENSIVE RATS. (January 2023)

• Record Type: Journal Article
• Authors: Rahman, Asadur; Rahman, Asasur; Kidoguchi, Satoshi; Nourin, Jahan; Fujisawa, Yoshihide; Hossain, Akram; Steeve, Akumwami; Nakano, Daisuke; Kobara, Hideki; Masaki, Tsutomu; Kitada, Kento; Nishiyama, Akira
• Is Part Of: Journal of hypertension. Volume 41(2023)Supplement 1
• Page Start: e270
• Publication Date: 2023-01
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000915484.28731.6c
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Background: We have recently shown that the nonsteroidal mineralocorticoid receptor blocker, esaxerenone elicits effective blood pressure reduction in Dahl salt-sensitive hypertensive (DSS) rats. Here, we investigated the potential contribution of alterations in sodium homeostasis to esaxerenone-induced blood pressure reduction. Methods: In the different experimental setups, we evaluated blood pressure by the radio-telemetry system and sodium homeostasis by an approach of sodium in (food intake) and out (urinary excretion) in a low-salt diet (LSD, 0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD with 0.001 % esaxerenone (w/w), and HSD with 0.05% furosemide fed DSS rats. Results: HSD-fed DSS rats exhibited a non-dipper type hypertension, while esaxerenone treatment but not furosemide significantly reduced the BP with a dipper pattern. The cumulative urinary sodium excretion was significantly elevated from day 6 onward both in esaxerenone- and furosemide-treated rats compared to their HSD-fed counterparts in the active period where a significant increase in Na+/K+ ratio was evident for only the esaxerenone treatment group. Sodium content in the skin, skinned carcass as well as total body level tended to reduce in esaxerenone-treated rats compared to the HSD-fed matching parts, while these values were not changed in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation revealed that esaxerenone but not furosemide treatment significantly attenuated glomerulosclerosis and tubulointerstitial fibrosis in HSD-fed DSS rats. Collectively, these findings suggest that esaxerenone-induced blood pressure reduction is associated with the body sodium homeostasis in salt-loaded DSS rats.