Role of the α1D-adrenegric receptor in the development of salt-induced hypertension

被引:48
作者
Tanoue, A
Koba, M
Miyawaki, S
Koshimizu, T
Hosoda, C
Oshikawa, S
Tsujimoto, G
机构
[1] Natl Ctr Child Hlth & Dev Res Inst, Dept Mol Cell Pharmacol, Setagaya Ku, Tokyo 1548567, Japan
[2] Nippon Shinyaku Co Ltd, Discovery Res Labs, Tsukuba, Ibaraki, Japan
关键词
receptors; adrenergic; mice; hypertension; sodium-dependent; nephrectomy;
D O I
10.1161/01.HYP.0000022062.70639.1C
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
In an attempt to elucidate whether there is a specific alpha(1)-adrenergic receptor (alpha(1)-AR) subtype involved in the genesis or maintenance of hypertension, the alpha(ID)-AR subtype was evaluated in a model of salt-induced hypertension. The alpha(1D)-AR-deficient (alpha(1D)) and control (alpha(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 alpha(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 (alpha(1D)(+/+)), from a baseline 97.4 +/- 2.9 to an end point 139.4 +/- 4.5 mm Hg. Seven of 15 alpha(1D)(+/+) mice died with edema, probably owing to renal failure, whereas 14 of 15 alpha(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 alpha(1D)(+/+) than in the alpha(1D)(-/-) mice. These data suggest that aID-AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective alpha(1D)-AR antagonism could have significant therapeutic potential in the treatment of hypertension.
引用
收藏
页码:101 / 106
页数:6
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