Role of α2-adrenergic receptor subtypes in the acute hypertensive response to hypertonic saline infusion in anephric mice

Abstract

Experimental 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 (α(2A)-, α(2B), - and α(2C)-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 α(2A)-AR-deficient and α(2C)-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 α(2B) +/+ (13.1±2.4 mm Hg). However, the α(2B)-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 α(2B)-AR-deficient mice, which, despite the elevated norepinephrine, were unable to raise their BP. The data suggest that a full complement of the α(2B)-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.