title: Clonidine improves spontaneous baroreflex sensitivity in conscious mice through parasympathetic activation.
abstract: Alpha-2 adrenoceptors are important in baroreflex regulation. We tested the impact of alpha-2 adrenoceptors on heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS) in conscious mice with telemetry (TA11PA-C20). Baseline beat-to-beat measurements (2 hours between 8:00 am to 12:00 pm) were compared with measurements after intraperitoneal alpha-2 adrenoceptor blockade (yohimbine 2 mg/kg) and alpha-2 adrenoceptor stimulation (clonidine 1, 10, and 50 mg/kg). Blood pressure (BP) was 128+/-6/87+/-6 mm Hg and heart rate (HR) was 548+/-18 bpm at baseline. BRS, calculated with the cross-spectral method, was 1.2+/-0.1 ms/mm Hg at baseline. BP increased 20+/-2/13+/-2 mm Hg with yohimbine. HR increased by 158+/-23 bpm. BRS did not change. BP decreased 16+/-7/5+/-4 mm Hg with 1 mg/kg of clonidine and did not change with a higher dose. HR decreased with clonidine (176+/-28, 351+/-21, 310+/-29 bpm during 1, 10, and 50 mg/kg of clonidine, P<0.01). HRV (total power=4629+/-465, 7002+/-440, and 6452+/-341 ms2 during 1, 10, and 50 mg/kg of clonidine, P<0.01) and BRS were profoundly increased with clonidine (14+/-1, 13+/-1, and 10+/-1 ms/mm Hg, P<0.01). The effects of clonidine were abolished with atropine (2 mg/kg plus 50 mg/kg of clonidine) but not with metoprolol (4 mg/kg plus 50 mg/kg of clonidine). These data suggest that alpha-2 adrenoceptors exert a regulatory influence on autonomic cardiovascular control and baroreflex function. The effect of clonidine on baroreflex HR regulation is mediated by the parasympathetic nervous system. These murine data fit well with recent human observations regarding parasympathetic activation via alpha-2 adrenoceptors.
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: Jens
authors.initials: J
authors.lastname: Jordan
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.forename: Michael
authors.initials: M
authors.lastname: Obst
authors.forename: Ralph
authors.initials: R
authors.lastname: Plehm
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gross
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D003243:Consciousness; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008991:Monitoring, Physiologic / Q000379:methods; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D012119:Respiration / Q000187:drug effects; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013686:Telemetry; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D015016:Yohimbine; D008790:Metoprolol; D003000:Clonidine