Role of α2-Adrenergic Receptor Subtypes in the Acute Hypertensive Response to Hypertonic Saline Infusion in Anephric Mice

ABSTRACTExperimental evidence suggests that the acute hypertensive response induced in anephric animals by infusion of a hypertonic saline solution is mediated by disinhibition of the presynaptic sympathoinhibitory α2-adrenergic receptors (α2-AR) of the central nervous system. The purpose of the present experiments was to dissect the role of the 3 distinct α2-AR subtypes (α2A-, α2B, - and α2C-AR) in this response. Groups of genetically engineered mice deficient in each one of these α2-AR subtype genes were submitted to bilateral nephrectomy followed by a 0.4-mL infusion of 4% saline over a 2-hour period, with constant direct blood pressure (BP) monitoring. The α2A-AR–deficient and α2C-AR–deficient mice responded with significant BP elevations (by 11.8±2.5 and 16.7±1.7 mm Hg, respectively), and so did their wild-type counterparts (17.8±2.5 and 11.8±2.0 mm Hg, respectively) and the wild-type α2B +/+ (13.1±2.4 mm Hg). However, the α2B-AR–deficient mice were unable to raise their BP and had a slightly lowered BP (by −3.0±4.0 mm Hg) at the end of the infusion period. All 6 groups exhibited elevated plasma norepinephrine levels ranging between 0.8 and 1.8 ng/mL at the end of the infusion. In all cases, the α2-AR–deficient groups tended to have higher norepinephrine levels than their wild-type counterparts. Surprisingly, this difference was significant only in the α2B-AR–deficient mice, which, despite the elevated norepinephrine, were unable to raise their BP. The data suggest that a full complement of the α2B-AR is needed to mediate the hypertensive response to acute saline load, even though its absence does not prevent the release of norepinephrine under these conditions.