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

In an attempt to elucidate whether there is a specific 1-adrenergic receptor ( 1-AR) subtype involved in the genesis or maintenance of hypertension, the 1D-AR subtype was evaluated in a model of salt-induced hypertension. The 1D-AR–deficient ( 1D / ) and control ( 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 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 ( 1D / ), from a baseline 97.4 2.9 to an end point 139.4 4.5 mm Hg. Seven of 15 1D / mice died with edema, probably owing to renal failure, whereas 14 of 15 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 1D / than in the 1D / mice. These data suggest that 1D-AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective 1D-AR antagonism could have significant therapeutic potential in the treatment of hypertension. (Hypertension. 2002;40:101-106.)