(Hypertension. 1999;33:14-17.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
2B-Adrenergic Receptor in the Development of Salt-Induced Hypertension
From the Hypertension and Atherosclerosis Section of the Department of Medicine, Boston University School of Medicine, Boston, Mass; and Stanford University (B.K.), Stanford, Calif.
Correspondence to Dr Haralambos Gavras, Hypertension & Atherosclerosis Section, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118. E-mail hgavras{at}bu.edu
AbstractSalt sensitivity is a
common trait in patients with essential hypertension and seems to have
both an inherited and an acquired component (eg, is influenced by aging
and renal insufficiency). Experimental evidence suggests that salt
loading induces hypertension via a neurogenic mechanism mediated by the
2-adrenergic receptors (
2-AR). To explore
the
2-AR subtype involved in this mechanism, we studied
2 groups of mice genetically engineered to be deficient in one of the 3
2-AR subtype genes (either
2B-AR
+/- or
2C-AR -/- knockout mice) compared with their
wild-type counterparts. The mice (n=10 to 14 in each group) were
submitted to subtotal nephrectomy and given 1% saline as drinking
water for up to 35 days. Blood pressure (BP) was monitored by tail-cuff
readings and confirmed at the end point by direct
intra-arterial BP recording. The
2B-ARdeficient mice had an attenuated BP response in
this protocol (baseline 101.8±2.7 versus end point 109.9±2.8
mm Hg), whereas the BP of their wild-type counterparts went from a
baseline 101.9±2.3 to an end point 141.4±7.1 mm Hg. The other 2
groups had BP increases of 44.6±5.17 and 46.7±7.01 mm Hg, with
no difference between the mice deficient in the
2C-AR
gene subtype versus their wild-type counterparts. Body weight, renal
remnant weight, and residual renal function were no different among
groups. These data suggest that a full complement of
2B-AR genes is necessary to raise BP in response to
dietary salt loading, whereas complete absence of the
2C-AR subtype does not preclude salt-induced BP
elevation. It is unclear whether the mechanism(s) involved in this
process are of central origin (inability to increase sympathetic
outflow), vascular origin (inability to vasoconstrict), or renal origin
(inability to retain excess salt and fluid).
Key Words: receptors, adrenergic, alpha mice hypertension, sodium-dependent
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