Influence of perillyl alcohol on human umbilical vein relaxation: mechanisms involving calcium channels and protein kinase C.

INTRODUCTION

Perillyl alcohol (POH) is a monoterpene found in the essential oil of several plants. Few studies have evaluated its effects on isolated vessels. Therefore, this study aimed to evaluate the effect of POH on human umbilical veins (HUV).

METHOD: The isometric tension of endothelium-denuded HUV rings was recorded in different functional assays in an organ bath. The effect of POH (1-2000 μM) was evaluated on the basal and active tone of the rings, and possible mechanisms of action at transmembrane and intracellular levels were proposed.

RESULTS

POH induced a biphasic effect on the basal tone of the rings and inhibited vasoconstriction mediated by depolarization (KCl 60 mM) and agonists (5-HT, His; 10 μM or BK; 0.1 μM). In Ca2+-free solution, POH inhibited vasoconstriction induced by BaCl2 (3-10 mM) and PMA (10 μM), but not 5-HT (10 μM). The potency and efficacy of the vasorelaxant effect of POH were not significantly modified in the presence of K+ channel blockers (TEA 1 or 10 mM, 4-AP 1 mM, or Gli 10 μM) and endothelial pathways blockers (L-NAME 1 mM or ODQ 100 μM).

DISCUSSION: Our findings suggest that the mode of action of POH in HUV involves transmembrane (blocking extracellular Ca2+ influx) and intracellular (inhibiting PKC) pathways, with less involvement of K+ channels and NOS and GC enzymes. Thus, the present study contributes to the discovery of new pharmacological candidates for disorders that increase umbilical vascular resistance.