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 Ca²⁺-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 Ca²⁺ stores by A23187 or ryanodine completely elimited the phenol-induced contractions. When caffeine (10 mM) and noradrenaline (NA, 10μM) were consecutively applied in Ca²⁺-free solution with an interval of 7 min (sufficient to prevent caffeine-induced inhibition of Ca²⁺ 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 Ca²⁺-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 Ca²⁺ release from intracellular Ca²⁺ 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. Presented in part at the annual meeting of the American Society of Anesthesiologists, Atlanta, Georgia October 21–25, 1995