Modulation of the baroreceptor reflex by alpha 2A-adrenoceptors: a study in alpha 2A knockout mice.
1. Our objective was to determine whether alpha(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 alpha(2A)-adrenoceptor-deficient (alpha(2A)-KO) mice and WT mice. 2. In conscious alpha(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 alpha(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 alpha(2A)-KO mice. The baroreceptor reflex gain upon volume loading was also low in anaesthetized alpha(2A)-KO mice. 5. The reflex tachycardia evoked by intravenous sodium nitroprusside injection was also significantly less in alpha(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 beta-adrenoceptors by the agonist isoprenaline produced similar cardioacceleration in alpha(2A)-KO and WT animals. 7. Our results show that the baroreceptor reflex function is impaired in mice lacking alpha(2A)-adrenoceptors. We conclude that central alpha(2A)-adrenoceptors facilitate the reflex response to both loading and unloading of the arterial baroreceptors.
Niederhoffer
Nathalie
N
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Freiburg, Albertstrasse 25, D-79104, Freiburg i Br, Germany. nathalie.niederhoffer@pharmakol.uni-freiburg.de
Hein
Lutz
L
Starke
Klaus
K
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009599:Nitroprusside / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis* / Q000172:deficiency*
C547769:Adra2a protein, mouse; D018341:Receptors, Adrenergic, alpha-2; D009599:Nitroprusside