Attenuation of haemodynamic, metabolic and energy expenditure responses to isoproterenol in patients with hypertension.
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.
Valentini
Mariaconsuelo
M
Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
Julius
Stevo
S
Palatini
Paolo
P
Brook
Robert D
RD
Bard
Robert L
RL
Bisognano
John D
JD
Kaciroti
Niko
N
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
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol