α2B‐Adrenergic receptor deficiency modulates DOCA‐salt hypertension

Studies suggest central nervous system (CNS) α 2B ‐adrenoceptors (α 2B ‐AR) regulate blood pressure (BP), renal sympathetic nervous system activity (SNSA) and salt balance. However, it is not clear whether CNS α 2B ‐AR subtypes lower BP and SNSA or contribute to salt‐induced increases in BP and SNSA. Infusing nonselective α 2 ‐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 α 2B ‐AR activate RSNA and contribute to DOCA‐salt‐induced increases in BP. HET and WT α 2B ‐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 α 2B ‐AR appear necessary for the reflex decrease in HR and NE excretion during the development of DOCA‐salt hypertension suggesting that CNS α 2B ‐AR modulate SNSA responses to salt loading and increased BP.