Norepinephrine release during autoregulatory escape: Effects of α₂-receptor blockade

The partial recovery that intestinal blood flow undergoes during continued sympathetic nerve stimulation is termed autoregulatory escape. This study tested two hypotheses that might explain escape: 1) diminishing norepinephrine (NE) release during sustained stimulation and 2) an α₂-receptor-mediated competition between local and neural control mechanisms. The rates of NE release before and during stimulation of the perivascular sympathetic nerves were determined by measuring blood flow in isolated loops of canine small intestine and assaying the concentrations of NE in arterial and venous blood. The presence of functional α₂-receptors was demonstrated by clonidine injections, and the effects of α₂-receptor blockade were studied during yohimbine infusions. The time course of NE release was inconsistent with a cause-effect relationship; NE release was greatest during the phase when resistance had already escaped. Deliberately altering NE release by changing the stimulus duration did not affect escape. The study demonstrated 1) that diminished NE release during continued sympathetic stimulation does not occur and cannot account for escape, 2) that resistance vessels in the canine intestinal circulation possess functional α₂-receptors which are responsible for part of the vasoconstriction caused by sympathetic stimulation, 3) that blockade of presynaptic α₂-receptors significantly enhanced NE release during the initial 30-s period but not during the escape phase, and 4) that α₂-receptor blockade enhances autoregulatory escape. Altogether these findings indicate that the postsynaptic α₂-receptors on intestinal resistance vessels deserve further investigation as the possible site at which local and neural mechanisms compete to influence vascular resistance.