Decreased blood pressure response in mice deficient of the alpha(1b)-adrenergic receptor

To investigate the functional role of different alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the alpha(1b)-AR (alpha(1b)-/-). Reverse transcription-PCR and ligand binding studies were combined to elucidate the expression of the alpha(1)-AR subtypes in various tissues of alpha(1b) +/+ and -/- mice. Total alpha(1)-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the alpha(1b) -/- as compared with +/+ mice. Because of the large decrease 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 and in vitro aorta contractile responses to alpha(1) agonists were investigated in alpha(1b) +/+ and -/- mice. Our findings provide strong evidence that the (alpha(1b)-AR is a mediator of the blood pressure and the aorta contractile responses induced alpha(1) agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in alpha(1b) -/- as compared with +/+ mice. In addition, phenylephrine-induced contractions of aortic rings also were decreased by 25% in alpha(1b) -/- mice. The alpha(1b)-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different alpha(1)-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.