Prejunctional alpha 2-adrenoceptors and norepinephrine release in the forearm of normal humans

To investigate the prejunctional alpha 2-adrenoceptor-mediated autoinhibitory feedback for norepinephrine (NE) release, we measured the response of forearm blood flow (FAF, mercury in silastic strain gauge plethysmography) and changes of the forearm venous-arterial NE difference (delta VA-NE, deep forearm vein, brachial artery norepinephrine concentration) induced by six intrabrachial artery 5-min infusions of clonidine in 13 normal volunteers. NE spillover into the forearm circulation was estimated as the product of delta VA-NE and FAF after three clonidine infusions. Clonidine caused dose-dependent decreases in FAF with a maximum reduction of FAF after the highest dose of clonidine of 32 +/- 8%, (N = 7, p less than 0.01) indicating postjunctional alpha-adrenergic stimulation. delta VA-NE increased slightly yet calculated norepinephrine spillover remained statistically unchanged after clonidine. The results suggest that auto-inhibitory feedback control of neuronal transmitter release via prejunctional alpha 2-adrenoceptors may not to an important degree modulate norepinephrine release in the forearm vasculature of healthy subjects.