Effects of moderate acidosis on adrenergic neurotransmission in canine saphenous veins

Abstract

Local acidosis depresses vascular smooth muscle reactivity. Experiments were performed to determine whether moderate acidosis also affects the release of norepinephrine in the blood vessel wall. Helical strips of dog saphenous veins were mounted for isometric tension recording; moderate metabolic acidosis (from pH 7.4 to 7.1) was obtained by lowering the HCO3 - concentration of the Krebs-Ringer solution at constant PCO2. Acidosis significantly reduced the contractile responses to sympathetic nerve stimulation (1-10 Hz), but not those to exogenous norepinephrine (10-8 - 10-4 M). The blocker of neuronal reuptake, cocaine (3 x 10-5 M), did not affect the depressant effect of acidosis on the response to nerve stimulation. Strips were incubated in solutions containing [3H]norepinephrine and mounted for superfusion and isometric tension recording; the overflow of [3H]norepinephrine and its metabolites in the superfusate was determined by column chromatography. In control strips, acidosis caused relaxation during nerve stimulation, but did not significantly alter the evoked release of labeled transmitter; by contrast, in strips treated with cocaine, acidosis depressed the contractile response and the overflow of [3H]norepinephrine to the same extent. In the absence of cocaine, acidosis depressed the release of norepinephrine evoked by 50 mEq/l of K+, but not its displacement by 6 x 10-5 M tyramine. Acidosis significantly depressed the tissue uptake of [3H]norepinephrine, determined by extraction and column chromatography; it did not significantly alter the inhibitory effect of cocaine on [3H]norepinephrine uptake. These experiments provide direct evidence that moderate variations in extracellular pH can inhibit the evoked release of norepinephrine and suggest that local acidosis may participate in the functional disconnection of the blood vessels of metabolically active tissues from sympathetic control. They further support the concept that there is a temporal dissociation between the release of norepinephrine and its reuptake by the adrenergic nerve endings.