Role of the alpha1D-adrenergic receptor in the development of salt-induced hypertension.
In an attempt to elucidate whether there is a specific alpha1-adrenergic receptor (alpha1-AR) subtype involved in the genesis or maintenance of hypertension, the alpha1D-AR subtype was evaluated in a model of salt-induced hypertension. The alpha1D-AR-deficient (alpha1D-/-) and control (alpha1D+/+) 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 alpha1D-/- 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 (alpha1D+/+), from a baseline 97.4+/-2.9 to an end point 139.4+/-4.5 mm Hg. Seven of 15 alpha1D+/+ mice died with edema, probably owing to renal failure, whereas 14 of 15 alpha1D-/- 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 alpha1D+/+ than in the alpha1D-/- mice. These data suggest that alpha1D-AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective alpha1D-AR antagonism could have significant therapeutic potential in the treatment of hypertension.
Tanoue
Akito
A
Department of Molecular, Cell Pharmacology, National Center for Child Health and Development Research Institute, Tokyo, Japan.
Koba
Masahiro
M
Miyawaki
Shigeki
S
Koshimizu
Taka-aki
TA
Hosoda
Chihiro
C
Oshikawa
Sayuri
S
Tsujimoto
Gozoh
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D015996:Survival Rate
C547720:Adra1d protein, mouse; D002395:Catecholamines; D018340:Receptors, Adrenergic, alpha-1; D017673:Sodium Chloride, Dietary