Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c.
alpha2-Adrenergic receptors (alpha2ARs) are essential components of the neural circuitry regulating cardiovascular function. The role of specific alpha2AR subtypes (alpha2a, alpha2b, and alpha2c) was characterized with hemodynamic measurements obtained from strains of genetically engineered mice deficient in either alpha2b or alpha2c receptors. Stimulation of alpha2b receptors in vascular smooth muscle produced hypertension and counteracted the clinically beneficial hypotensive effect of stimulating alpha2a receptors in the central nervous system. There were no hemodynamic effects produced by disruption of the alpha2c subtype. These results provide evidence for the clinical efficacy of more subtype-selective alpha2AR drugs.
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RE
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Desai
K
K
Hein
L
L
Stevens
M E
ME
Chruscinski
A
A
Bernstein
D
D
Barsh
G S
GS
Kobilka
B K
BK
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018390:Gene Targeting; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D020926:Medetomidine; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000502:physiology*; D015016:Yohimbine / Q000378:metabolism
C547775:Adra2c protein, mouse; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D015016:Yohimbine; D020926:Medetomidine; D011224:Prazosin