Role of the α 1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

Abstract

In an attempt to elucidate whether there is a specific α 1 -adrenergic receptor (α 1 -AR) subtype involved in the genesis or maintenance of hypertension, the α 1D -AR subtype was evaluated in a model of salt-induced hypertension. The α 1D -AR–deficient (α 1D −/− ) and control (α 1D +/+ ) mice (n=8 to 14 in each group) were submitted to subtotal nephrectomy and given 1% saline as drinking water for 35 days. Blood pressure (BP) was monitored by tail-cuff readings and confirmed at the end point by direct intraarterial BP recording. The α 1D −/− mice had a significantly ( P =0.0004) attenuated increase in BP response in this protocol (baseline 94.6±2.8 versus end point 107.4±4.5 mm Hg) compared with that of their wild-type counterparts (α 1D +/+ ), from a baseline 97.4±2.9 to an end point 139.4±4.5 mm Hg. Seven of 15 α 1D +/+ mice died with edema, probably owing to renal failure, whereas 14 of 15 α 1D −/− mice were maintained for 35 days. Body weight, renal remnant weight, and residual renal function were similar in the 2 groups, whereas the values of plasma catecholamines (epinephrine, norepinephrine, and dopamine) were higher in α 1D +/+ than in the α 1D −/− mice. These data suggest that α 1D -AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective α 1D -AR antagonism could have significant therapeutic potential in the treatment of hypertension.