Role of the alpha1D-adrenergic receptor in the development of salt-induced hypertension.

Abstract

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.

• Authors: Akito Tanoue, Masahiro Koba, Shigeki Miyawaki, Taka-aki Koshimizu, Chihiro Hosoda, Sayuri Oshikawa, Gozoh Tsujimoto
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 40 Issue 1 Pg. 101-6 (Jul 2002) ISSN: 1524-4563 [Electronic] United States
• PMID: 12105146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adra1d protein, mouse
• Catecholamines
• Receptors, Adrenergic, alpha-1
• Sodium Chloride, Dietary

Topics

• Animals
• Blood Pressure (drug effects)
• Catecholamines (blood)
• Genotype
• Heart Rate (drug effects)
• Hypertension (chemically induced, mortality, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Nephrectomy
• Receptors, Adrenergic, alpha-1 (genetics, physiology)
• Sodium Chloride, Dietary (administration & dosage)
• Survival Rate