Cardiovascular Regulation in Mice Lacking α 2 -Adrenergic Receptor Subtypes b and c

• DOI: 10.1126/science.273.5276.803
• Publication Date: 2006-10-27T18:30:41Z
• Authors: Richard E. Link; Kavin Desai; Lutz Hein; Mary E. Stevens; Andrzej Chruscinski; Daniel Bernstein; Gregory S. Barsh; Brian K. Kobilka
• Keywords: Mice, Knockout; 0301 basic medicine; Imidazoles; Yohimbine; Blood Pressure; Mice, Inbred Strains; Prazosin; Medetomidine; Kidney; Muscle, Smooth, Vascular; 3. Good health; Mice, Inbred C57BL; Mice; Phenylephrine; 03 medical and health sciences; Heart Rate; Receptors, Adrenergic, alpha-2; Gene Targeting; Animals; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists

α 2 -Adrenergic receptors (α 2 ARs) are essential components of the neural circuitry regulating cardiovascular function. The role of specific α 2 AR subtypes (α 2a , α 2b , and α 2c ) was characterized with hemodynamic measurements obtained from strains of genetically engineered mice deficient in either α 2b or α 2c receptors. Stimulation of α 2b receptors in vascular smooth muscle produced hypertension and counteracted the clinically beneficial hypotensive effect of stimulating α 2a receptors in the central nervous system. There were no hemodynamic effects produced by disruption of the α 2c subtype. These results provide evidence for the clinical efficacy of more subtype-selective α 2 AR drugs.