title: Attenuation of haemodynamic, metabolic and energy expenditure responses to isoproterenol in patients with hypertension.
abstract: OBJECTIVE
  Overweight and heightened sympathetic activity are more common in hypertensive than normotensive subjects. beta-adrenoceptor down-regulation has been described in hypertension. We tested the hypothesis that chronic sympathetic overactivity impairs beta-adrenergic-mediated thermogenesis and thereby favours gain of weight in hypertension.
  
  
  METHODS
  The study included 13 hypertensive subjects aged 35.3 +/- 7.9 years and 25 normotensive subjects of control of similar age.
  
  
  METHODS
  To measure beta-adrenergically mediated haemodynamic, metabolic and thermogenic responsiveness, increasing doses of isoproterenol diluted in 2.5 ml saline were injected as intravenous boluses (0.1, 0.25, 0.5, 1.0 and 2.0 microg/m). On a separate day, isoproterenol was infused continuously intravenously in increasing doses (10, 20 and 40 ng/kg per min), each dose for 30 min.
  
  
  RESULTS
  The sitting heart rate and body mass were greater in hypertensives (P = 0.000, and P = 0.005, respectively). The heart rate responses to 1 and 2 microg/m isoproterenol bolus (P = 0.01 and P = 0.03, respectively) were reduced in hypertensives. The energy expenditure (P = 0.002) and oxygen consumption (P = 0.0004) increase with 40 ng/kg per min isoproterenol infusion, and glucose and phosphate responses at both 20 (P = 0.01 and P = 0.05) and 40 (P = 0.001 and P = 0.02) ng/kg per min isoproterenol infusion were attenuated in hypertensives. The baseline heart rate negatively correlated with heart rate (P = 0.015) response to isoproterenol bolus and blood pressure (P = 0.02) response to isoproterenol infusion. The urinary noradrenaline negatively correlated with heart rate response to isoproterenol bolus (P = 0.001), and with systolic blood pressure (P = 0.02) and energy expenditure responsiveness to isoproterenol infusion (P = 0.04). Furthermore, plasma noradrenaline negatively correlated with heart rate responsiveness to isoproterenol bolus (P = 0.004).
  
  
  CONCLUSIONS
  These results show a generalized decrease of beta-adrenergic responsiveness in stage 1 hypertension and support the concept that sympathetic overactivity, via down-regulation of beta-adrenoceptor-mediated thermogenic responses, may facilitate the development of obesity in hypertension.
authors.affiliation: Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Mariaconsuelo
authors.initials: M
authors.lastname: Valentini
authors.forename: Stevo
authors.initials: S
authors.lastname: Julius
authors.forename: Paolo
authors.initials: P
authors.lastname: Palatini
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brook
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bard
authors.forename: John D
authors.initials: JD
authors.lastname: Bisognano
authors.forename: Niko
authors.initials: N
authors.lastname: Kaciroti
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D004734:Energy Metabolism / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol