Modulation of the baroreceptor reflex by α2A-adrenoceptors: a study in α2A knockout mice

Our objective was to determine whether α2A-adrenoceptors modulate the baroreceptor reflex. The efficacy of the reflex was evaluated by measuring the spontaneous blood pressure and heart rate variability at rest and the heart rate responses to evoked changes in blood pressure. Experiments were carried out in conscious, unrestrained, and anaesthetized α2A-adrenoceptor-deficient (α2A-KO) mice and WT mice. In conscious α2A-KO mice, the spontaneous blood pressure variability was greater, and the spontaneous heart rate variability was lower than in conscious WT mice. This was also observed in anaesthetized animals. The reflex bradycardia after intravenous injection of phenylephrine was greatly attenuated in conscious α2A-KO compared to conscious WT mice; the baroreceptor reflex gain (ratio maximal change in heart rate/maximal change in mean arterial pressure) was decreased by 40%. Similar results were obtained when reflex bradycardia was elicited by intra-arterial volume loading of conscious WT and α2A-KO mice. The baroreceptor reflex gain upon volume loading was also low in anaesthetized α2A-KO mice. The reflex tachycardia evoked by intravenous sodium nitroprusside injection was also significantly less in α2A-KO mice as compared to WT, conscious as well as anaesthetized; the baroreceptor reflex gains were decreased by 50 and 65%, respectively. Direct stimulation of cardiac β-adrenoceptors by the agonist isoprenaline produced similar cardioacceleration in α2A-KO and WT animals. Our results show that the baroreceptor reflex function is impaired in mice lacking α2A-adrenoceptors. We conclude that central α2A-adrenoceptors facilitate the reflex response to both loading and unloading of the arterial baroreceptors. British Journal of Pharmacology (2004) 141, 851–859. doi:10.1038/sj.bjp.0705636