α₂ and α₁, -adrenergic receptors in regulation of peripheral vascular function

Specific aspects of the regulation of peripheral and central vascular function by subtypes of the α₂-adrenergic receptor (AR) have been studied . To evaluate the contribution of the α_2A-AR a genetically modified mouse line was developed by homologous recombination. The mutation, D79Na_2AAR, substitutes an asparagine for an aspartate at position 79 of the amino acid sequence of the receptor. Resting mean arterial blood pressure (MAP) or heart rate in D79N mutant animals was not different when compared to wildtype. In wild-type animals, infusion of UK 14304 produced a dosedependent increase in MAP which was followed by hypotension which lasted for 3 hrs. In contrast, UK 14304 had no pressor effect in D79N mutants nor was the long lasting hypotension observed. In the isolated wild-type and D79N aorta, UK 14304 produced a concentration dependent increase in contractile tension which was antagonized by prazosin. However, the maximal response in mutant aorta was significantly less than that seen in the wild-type. These data suggest the α_2A-AR plays a prominent role in peripheral as well as central cardiovascular regulation.