DECREASED BLOOD-PRESSURE RESPONSE IN MICE DEFICIENT OF THE ALPHA(1B)-ADRENERGIC RECEPTOR

To investigate the functional role of different alpha(1)-adrenergic re ceptor (alpha(1)-AR) subtypes in vivo, we have applied a gene targetin g approach to create a mouse model lacking the alpha(1b)-AR (alpha(1b) -/-). Reverse transcription-PCR and ligand binding studies were combin ed to elucidate the expression of the alpha(1)-AR subtypes in various tissues of alpha(1b) +/+ and -/- mice. Total alpha(1)-AR sites were de creased by 98% in liver, 74% in heart, and 42% in cerebral cortex of t he alpha(1b) -/- as compared with +/+ mice. Because of the large decre ase of alpha(1)-AR in the heart and the loss of the (alpha(1b)-AR mRNA in the aorta of the alpha(1b) -/- mice, the in vivo blood pressure an d in vitro aorta contractile responses to alpha(1) agonists were inves tigated in alpha(1b) +/+ and -/- mice. Our findings provide strong evi dence that the (alpha(1b)-AR is a mediator of the blood pressure and t he aorta contractile responses induced alpha(1) agonists. This was dem onstrated by the finding that the mean arterial blood pressure respons e to phenylephrine was decreased by 45% in alpha(1b) -/- as compared w ith +/+ mice. In addition, phenylephrine-induced contractions of aorti c rings also were decreased by 25% in alpha(1b) -/- mice. The alpha(1b )-AR knockout mouse model provides a potentially useful tool to elucid ate the functional specificity of different alpha(1)-AR subtypes, to b etter understand the effects of adrenergic drugs, and to investigate t he multiple mechanisms involved in the control of blood pressure.