DESIPRAMINE BLOCKS AUGMENTED NEUROGENIC VASOCONSTRICTOR RESPONSES TO EPINEPHRINE

The forearm vasoconstrictor response to lower body negative pressure (LBNP), a reflex stimulus to norepinephrine release, can be augmented by a prior brachial artery infusion of epinephrine. We wished to determine whether this sustained aftereffect of epinephrine could be replicated by systemic infusion and, if so, whether it could be prevented by prior uptake-1 blockade with desipramine. Eight normal men (mean age 30 years) were studied on two separate study days at least 1 week apart, 2.5 hours after taking, at random, either desipramine (125 mg p.o.) or placebo. Forearm vascular resistance was measured at rest and at the end of 6 minutes of LBNP at -40 mm Hg. This was done both before and 30 minutes after a 60-minute infusion of epinephrine (1.5 μg/min i.v.). From similar baselines, the forearm vasoconstrictor response to LBNP was significantly augmented 30 minutes after epinephrine on the placebo day (+17±4 vs. +12±3 resistance units, mean±SEM, p<0.01) but not on the desipramine day (+14±2 vs. +16±3 resistance units). The heart rate response to LBNP was also greater after epinephrine on the placebo day (+20±3 vs. +16±2 beats/min,p<0.05). Mean arterial pressure was higher after epinephrine infusion on the placebo (p<0.01) but not on the desipramine day. Thus, transient increases in epinephrine, which has a plasma half-life of only minutes, can have sustained aftereffects, increasing mean arterial pressure and augmenting vasoconstrictor and chronotropic responses to a reflex stimulus to norepinephrine release 30 minutes after its infusion. These effects appear to be mediated through the uptake of epinephrine by sympathetic nerves and its corelease with norepinephrine on subsequent nerve stimulation. Epinephrine then could act on prejunctional β-adrenergic receptors to facilitate norepinephrine release and augment neurogenic vasoconstriction. These observations provide further support for the concept that increases in plasma epinephrine concentration might contribute to the pathogenesis of essential hypertension by this mechanism.