Modulation of the baroreceptor reflex by α_2A‐adrenoceptors: a study in α_2A knockout mice

Abstract

1 Our objective was to determine whether a 2A -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 a 2A -adrenoceptor-deficient (a 2A -KO) mice and WT mice. 2 In conscious a 2A -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. 3 The reflex bradycardia after intravenous injection of phenylephrine was greatly attenuated in conscious a 2A -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%. 4 Similar results were obtained when reflex bradycardia was elicited by intra-arterial volume loading of conscious WT and a 2A -KO mice. The baroreceptor reflex gain upon volume loading was also low in anaesthetized a 2A -KO mice. 5 The reflex tachycardia evoked by intravenous sodium nitroprusside injection was also significantly less in a 2A -KO mice as compared to WT, conscious as well as anaesthetized; the baroreceptor reflex gains were decreased by 50 and 65%, respectively. 6 Direct stimulation of cardiac b-adrenoceptors by the agonist isoprenaline produced similar cardioacceleration in a 2A -KO and WT animals. 7 Our results show that the baroreceptor reflex function is impaired in mice lacking a 2A -adrenoceptors. We conclude that central a 2A -adrenoceptors facilitate the reflex response to both loading and unloading of the arterial baroreceptors.

Do Allelic Variants in α 2A and α 2C Adrenergic Receptors Predispose to Hypertension in Blacks?

“…10 Targeted disruption of the ␣ 2 AR gene causes hypertension and tachycardia and impaired baroreceptor reflexes in mice. 21 The same phenotype is seen in mice with a point mutation in the ␣ 2 AR gene that reduces receptor density in the central nervous system to 20% of normal values. 22 Similarly, in humans, the DraI RFLP allele, which is present in 30% of blacks, might decrease ␣ 2A AR density and increase sympathetic activity, thereby predisposing to hypertension.…”

Abnormal Sympathoadrenal Development and Systemic Hypotension in PHD3−/− Mice

“…A subset of these mice were used to test baroreceptor reflex function by intravenous bolus administration of the ␣ 1 -adrenoreceptor agonist phenylephrine hydrochloride (at 50 g/kg) to induce brief periods of elevated blood pressure (30). Baroreceptor reflex gain was calculated as the maximal change in heart rate over the maximal change in blood pressure.…”

Critical Pathways in Heart Function: Bis(2-chloroethoxy)methane-Induced Heart Gene Transcript Change in F344 Rats

“…Activation of these receptors result in positive inotropic effects and maintenance of cardiac output (Brede et al, 2002;Klouche et al, 2002;Niederhoffer et al, 2004). Thus, the down-regulation of the adra2 gene tranascript only at the high exposure level, suggests that in the 2 lower dose groups heart function was maintained in part because alpha 2 adrenergic receptor function was maintained.…”