title: Alpha-2 adrenergic transmission and human baroreflex regulation.
abstract: We observed earlier that central alpha-2 adrenoceptor stimulation in mice greatly augments parasympathetic tone. To test the effects in humans, we assessed autonomic vasomotor tone and baroreflex regulation in 9 normal young adults on 2 occasions, once with and once without clonidine. We determined heart rate (HR), beat-by-beat blood pressure (BP), and muscle sympathetic nerve activity. HR variability was analyzed in the time and frequency domain. Pharmacological baroreflex slopes were determined using incremental phenylephrine and nitroprusside infusions. Clonidine lowered resting BP (122+/-4/73+/-3 versus 100+/-7/55+/-3 mm Hg, P<0.01), muscle sympathetic nerve activity (18+/-3 versus 4+/-2 bursts/min, P<0.01), and HR (62+/-3 versus 56+/-3 bpm, P<0.05). The baroreflex heart rate curve was reset to much lower HR values and showed no saturation at low HR. HR variability profoundly increased during clonidine plus phenylephrine (total power: 3224+/-843 versus 8943+/-2329 ms2, P<0.05). High-frequency power was 1451+/-520 at baseline and 6720+/-2475 ms2 during baroreceptor loading (P<0.05). The low-frequency/high-frequency ratio decreased (1.94+/-0.41 versus 0.69+/-0.10, P<0.05). In contrast, clonidine reduced resting sympathetic vasomotor tone and shifted the operating point of the sympathetic baroreflex to a flat part of the sympathetic baroreflex curve. The shift decreased the ability of the baroreflex to withdraw sympathetic vasomotor tone during baroreflex loading. These baroreflex changes were associated with a moderate increase in phenylephrine responsiveness. We conclude that alpha-2 adrenoceptor stimulation has a differential effect on baroreflex HR and vasomotor regulation. alpha-2 Adrenoceptor stimulation greatly augments baroreflex-mediated bradycardia, most likely by parasympathetic activation.
authors.affiliation: Department of Nephrology and Hypertension, Franz-Volhard-Clinic, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Tank
authors.forename: Andre
authors.initials: A
authors.lastname: Diedrich
authors.forename: Elke
authors.initials: E
authors.lastname: Szczech
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D002316:Cardiotonic Agents / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D003080:Cold Temperature; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D010543:Peroneal Nerve / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D013318:Stroke Volume / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D018341:Receptors, Adrenergic, alpha-2; D009599:Nitroprusside; D010656:Phenylephrine; D011433:Propranolol; D003000:Clonidine