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—Salt sensitivity is a common trait in patients with essential hypertension and seems to have both an inherited and an acquired component (eg, is influenced by aging and renal insufficiency). Experimental evidence suggests that salt loading induces hypertension via a neurogenic mechanism mediated by the α₂-adrenergic receptors (α₂-AR). To explore the α₂-AR subtype involved in this mechanism, we studied 2 groups of mice genetically engineered to be deficient in one of the 3 α₂-AR subtype genes (either α_2B-AR +/− or α_2C-AR −/− knockout mice) compared with their wild-type counterparts. The mice (n=10 to 14 in each group) were submitted to subtotal nephrectomy and given 1% saline as drinking water for up to 35 days. Blood pressure (BP) was monitored by tail-cuff readings and confirmed at the end point by direct intra-arterial BP recording. The α_2B-AR–deficient mice had an attenuated BP response in …