Effects of phenol on vascular smooth muscle in rabbit mesenteric resistance arteries.

Although phenol has long been used clinically as a neurolytic agent or as a preservative for injections, little information is available regarding its direct vascular action. We therefore studied the effects of phenol (0.1 μM-2mM) on isolated rabbit small mesenteric arteries, using isometric tension recording methods. All experiments were performed on endothelium-denuded strips. Phenol (≥10 μM) generated transsient contractions in a concentration-dependent manner in both normal Krebs and Ca(2+)-free solutions with EC50 values (concentrations that produced 50% of the maximal response) of 39.8 μM and 99.7 μM, respectively. Depletion of intracellular Ca(2+) stores by A23187 or ryanodine completely elimited the phenol-induced contractions. When caffeine (10 mM) and noradrenaline (NA, 10μM) were consecutively applied in Ca(2+)-free solution with an interval of 7 min (sufficient to prevent caffeine-induced inhibition of Ca(2+) sensitivity), caffeine eliminated the contractions induced by subsequent application of NA. In similar experiments where phenol (1 mM) and NA (10 μM) were consecutively applied in Ca(2+)-free solution, phenol significantly inhibited contractions induced by subsequent application of NA. Phenol (0.1 mM, ∼EC65), applied in the presence of either 128 mM K(+) or NA (10 μM), produced transient vasoconstrictions superimposed on both high K(+)-and NA-induced contractions, but had a lesser effect on maintenance of these contractions. The vascular responses to high K(+), NA, and caffeine after washout of phenol were not significantly different from those before application of phenol (up to 2 mM). The results suggest that phenol stimulates Ca(2+) release from intracellular Ca(2+) stores, which are sensitive to both caffine and NA in this resistance artery. The effect does not appear to reflect a toxic effect on vascular smooth muscle. It seems unlikely that phenol causes adverse hemodynamic changes because of the observed direct vascular action.