Twenty-four hour pressor effect of infused adrenaline in normotensive subjects: a randomized controlled double-blind cross-over study.
Stimulation of prejunctional beta 2-adrenoceptors on sympathetic nerve terminals increases vasoconstrictor nerve activity by facilitating release of noradrenaline. Therefore, man's endogenous beta 2-adrenoceptor agonist adrenaline has been implicated in the pathogenesis of hypertension. To test this hypothesis, adrenaline (15 mg/kg per min), noradrenaline (30 ng/kg per min) and saline (0.9% NaCl, 5.4 ml/h) were infused in 10 supine, resting healthy volunteers for 6 h (1000-1600 h) in random order 2 weeks apart in a double-blind crossover fashion. During infusion of noradrenaline and adrenaline, venous plasma concentrations rose to 705 +/- 58 (mean +/- s.e.m) and 230 +/- 28 pg/ml, respectively. Mean arterial pressure rose by 4% (P less than 0.001) during noradrenaline and fell by 5% (P less than 0.001) during the adrenaline infusion compared with the saline infusion. In the postinfusion period (1600-0900 h) mean arterial pressure was 7% higher (P less than 0.01) after adrenaline compared with the saline infusion, whereas after the noradrenaline infusion, values of mean arterial pressure were not different from those during the saline infusion. The pressor effect of adrenaline could not be explained by a central mechanism or by activation of the renin-angiotensin system. Thus, 'stress levels' of adrenaline mediate a delayed and protracted pressor effect. This is most likely due to stimulation of prejunctional beta 2-adrenoceptors, since 'stress levels' of noradrenaline are devoid of such activity. Our data support the 'adrenaline-hypertension' hypothesis in man.
Blankestijn
P J
PJ
Department of Internal Medicine I, Biostatistics, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Man in't Veld
A J
AJ
Tulen
J
J
van den Meiracker
A H
AH
Boomsma
F
F
Derkx
F H
FH
Moleman
P
P
van Eck
H J
HJ
Mulder
P
P
Lamberts
S W
SW
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D013997:Time Factors
D009638:Norepinephrine; D004837:Epinephrine