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(Hypertension. 2004;43:1042.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Clonidine Improves Spontaneous Baroreflex Sensitivity in Conscious Mice Through Parasympathetic Activation

Jens Tank; Jens Jordan; André Diedrich; Michael Obst; Ralph Plehm; Friedrich C. Luft; Volkmar Gross

From the Department of Nephrology and Hypertension (J.T., J.J., F.C.L.), Franz Volhard Clinic, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany; Autonomic Dysfunction Service (A.D.), Vanderbilt University, Nashville, Tenn; and the Max Delbrück Center for Molecular Medicine (J.J., M.O., R.P., F.C.L., V.G.), Berlin, Germany.

Correspondence to Dr Jens Jordan, Clinical Research Center, Haus 129, Franz-Volhard-Clinic, Medical Faculty of the Charité and HELIOS Klinikum Wiltbergstr. 50, 13125 Berlin, Germany. E-mail jordan{at}fvk.charite-buch.de

-2 Adrenoceptors are important in baroreflex regulation. We tested the impact of -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 -2 adrenoceptor blockade (yohimbine 2 mg/kg) and -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 -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 -2 adrenoceptors.

Key Words: antihypertensive agents • blood pressure • heart rate • baroreflex

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