The 'adrenaline hypothesis' of hypertension revisited: evidence for adrenaline release from the heart of patients with essential hypertension.
OBJECTIVE
Whether adrenaline acts as a sympathetic nervous cotransmitter in humans and stimulates beta2-adrenoceptors to augment neuronal noradrenaline release remains a subject of considerable dispute. The aim of this study was to test if adrenaline is released from regional sympathetic nerves (in the heart) in patients with essential hypertension, and to investigate whether locally released adrenaline might enhance cardiac noradrenaline release.


METHODS
Using dual isotope dilution methodology, adrenaline and noradrenaline plasma kinetics was measured for the whole body and in the heart in 13 untreated patients with essential hypertension and 27 healthy volunteers. All research participants underwent cardiac catheterization under resting conditions.


RESULTS
At rest, there was negligible adrenaline release from the sympathetic nerves of the heart in healthy subjects, 0.27 +/- 1.62 ng/min. In contrast, in patients with essential hypertension, adrenaline was released from the heart at a rate of 1.46 +/- 1.73 ng/min, equivalent on a molar basis to approximately 5% of the associated cardiac noradrenaline spillover value. Cardiac noradrenaline spillover was higher in hypertensive patients, 24.9 +/- 17.0 ng/min compared to 15.4 +/- 11.7 ng/min in healthy volunteers (P< 0.05). Among patients, rates of cardiac adrenaline and noradrenaline spillover correlated directly (r= 0.59, P< 0.05).


CONCLUSIONS
This study, in demonstrating release of adrenaline from the heart in patients with essential hypertension, and in disclosing a proportionality between rates of cardiac adrenaline and noradrenaline release, provides perhaps the most direct evidence to date in support of the 'adrenaline hypothesis' of essential hypertension.
Rumantir
M S
MS
Baker Medical Research Institute and Alfred Baker Medical Unit, Alfred Hospital, Melbourne, Australia. magdalena.rumantir@baker.edu.au
Jennings
G L
GL
Lambert
G W
GW
Kaye
D M
DM
Seals
D R
DR
Esler
M D
MD
D000328:Adult; D004837:Epinephrine / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006329:Heart Conduction System / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000378:metabolism
D009638:Norepinephrine; D004837:Epinephrine