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

To investigate the functional role of different α₁-adrenergic receptor (α₁-AR) subtypes in vivo, we have applied a gene targeting approach to create a mouse model lacking the α(1b)-AR (α(1b) -/-). Reverse transcription-PCR and ligand binding studies were combined to elucidate the expression of the α₁-AR subtypes in various tissues of α(1b) +/+ and -/- mice. Total α₁-AR sites were decreased by 98% in liver, 74% in heart, and 42% in cerebral cortex of the α(1b) -/- as compared with +/+ mice. Because of the large decrease of α₁-AR in the heart and the loss of the α(1b)-AR mRNA in the aorta of the α(1b) -/- mice, the in vivo blood pressure and in vitro aorta contractile responses to α₁-agonists were investigated in α(1b) +/+ and -/- mice. Our findings provide strong evidence that the α(1b)-AR is a mediator of the blood pressure and the aorta contractile responses induced by α₁ agonists. This was demonstrated by the finding that the mean arterial blood pressure response to phenylephrine was decreased by 45% in α(1b) -/- as compared with +/+ mice. In addition, phenylephrine- induced contractions of aortic rings also were decreased by 25% in α(1b) - /- mice. The α(1b)-AR knockout mouse model provides a potentially useful tool to elucidate the functional specificity of different α₁-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.