Role of the α _1D - Adrenegric Receptor in the Development of Salt-Induced Hypertension

Abstract

Abstract-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 Ϫ/Ϫ ) and control (␣ 1D ϩ/ϩ ) mice (nϭ8 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 Ϫ/Ϫ mice had a significantly (Pϭ0.0004) attenuated increase in BP response in this protocol (baseline 94.6Ϯ2.8 versus end point 107.4Ϯ4.5 mm Hg) compared with that of their wild-type counterparts (␣ 1D ϩ/ϩ ), from a baseline 97.4Ϯ2.9 to an end point 139.4Ϯ4.5 mm Hg. Seven of 15 ␣ 1D ϩ/ϩ mice died with edema, probably owing to renal failure, whereas 14 of 15 ␣ 1D Ϫ/Ϫ 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 ϩ/ϩ than in the ␣ 1D Ϫ/Ϫ 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.)

Blood Pressure Is Regulated by an α1D-Adrenergic Receptor/Dystrophin Signalosome

“…Although the ␣ 1D -AR is a key regulator of cardiovascular function (3,4), few studies have investigated the molecular characteristics of this important receptor. This is due to the difficulties in obtaining sufficient expression and function when expressed in vitro, because unlike the closely related ␣ 1A -and ␣ 1B -AR subtypes, the ␣ 1D -AR is retained intracellularly.…”

“…Each ␣ 1 -AR subtype (␣ 1A , ␣ 1B , and ␣ 1D ) signals through G␣ q/11 , activates phospholipase C␤ (PLC␤), and increases intracellular [Ca 2ϩ ] (1, 2). Despite ubiquitous expression, ␣ 1 -ARs are best characterized for their role in the cardiovascular system, where studies using ␣ 1 -AR knock-out (KO) have revealed a critical role in the regulation of blood pressure and cardiac function (3)(4)(5)(6). The role of ␣ 1 -ARs in the central nervous system is less clear, although expression in the brain has been implicated in regulating pyschostimulant effects of drugs of abuse, learning, and memory (2,7).…”

Polymorphisms of norepinephrine transporter and adrenergic receptor α1D are associated with the response to β-blockers in dilated cardiomyopathy

“…Several studies have investigated the possible associations between adrenergic receptor a 1D and hypertension. 8,9 In our subjects, no difference in blood pressure was observed among genotypes of ADRA1D T1848A and A1905G polymorphisms either before or after treatment. Therefore, these polymorphisms are likely to be associated with the drug response independently of blood pressure.…”

Dietary Sodium and Blood Pressure

“…17 In another rat model, Tanoue et al demonstrated a role of alpha receptors leading to an increase in blood pressure when challenged with a high-sodium diet. 18 Other investigators made important observations in other regulatory systems including the reninangiotensin system and others. 19 -23 The DASH Study investigators also demonstrated that the DASH diet, rich in fruits, vegetables, and low-fat dairy products, was natriuretic.…”