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 beta(2)- adrenoceptors to augment neuronal noradrena line release remains a subject of considerable dispute. The aim of this stu dy was to test if adrenaline is released from regional sympathetic nerves ( in the heart) in patients with essential hypertension, and to investigate w hether locally released adrenaline might enhance cardiac noradrenaline rele ase. Methods Using dual isotope dilution methodology, adrenaline and noradrenali ne plasma kinetics was measured for the whole body and in the heart in 13 u ntreated patients with essential hypertension and 27 healthy volunteers. Al l research participants underwent cardiac catheterization under resting con ditions. Results At rest, there was negligible adrenaline release from the sympathet ic nerves of the heart in healthy subjects, 0.27 +/- 1.62 ng/min. In contra st, in patients with essential hypertension, adrenaline was released from t he 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. C ardiac 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 spillov er correlated directly (r = 0.59, P < 0.05). Conclusions This study, in demonstrating release of adrenaline from the hea rt in patients with essential hypertension, and in disclosing a proportiona lity between rates of cardiac adrenaline and noradrenaline release, provide s perhaps the most direct evidence to date in support of the 'adrenaline hy pothesis' of essential hypertension. J Hypertens 2000, 18:717-723 (C) Lippi ncott Williams & Wilkins.