α2B‐Adrenergic receptor deficiency modulates DOCA‐salt hypertension

Abstract

Studies suggest central nervous system (CNS) α2B-adrenoceptors (α2B-AR) regulate blood pressure (BP), renal sympathetic nervous system activity (SNSA) and salt balance. However, it is not clear whether CNS α2B-AR subtypes lower BP and SNSA or contribute to salt-induced increases in BP and SNSA. Infusing nonselective α2-AR agonists centrally attenuates DOCA-salt-induced hypertension and renal SNS (RSN) activation. RSN ablation in rats also attenuates DOCA-salt hypertension. Therefore we hypothesized that α2B-AR activate RSNA and contribute to DOCA-salt-induced increases in BP. HET and WT α2B-AR KO mice were given DOCA-salt (50 mg implant sc, 1% NaCl, 1% KCl drinking water) or high-salt treatment (1% NaCl drinking water). BP and heart rate (HR) were recorded using telemetry for 4 control and 14 DOCA-salt or high-salt days. BP was significantly increased from control on days 1 to 14 of DOCA treatment in both WT and HET mice (p=0.02). High-salt only had no effect in either group. In contrast, HR was elevated in HET compared to control days and to WT mice during DOCA treatment (p<0.05). Urinary norepinephrine (NE) decreased with DOCA treatment in WT but not HET mice (p<0.05). Thus α2B-AR appear necessary for the reflex decrease in HR and NE excretion during the development of DOCA-salt hypertension suggesting that CNS α2B-AR modulate SNSA responses to salt loading and increased BP.