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

To investigate the functional role of different α(1)-adrenergic receptor (α(1)-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 α(1)-AR subtypes in various tissues of α(1b) +/+ and −/− mice. Total α(1)-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 α(1)-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 α(1)-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 α(1) 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 α(1)-AR subtypes, to better understand the effects of adrenergic drugs, and to investigate the multiple mechanisms involved in the control of blood pressure.