Carvacrol (CRV) is the main compound of essential oils extracted primarily from Thymus and Origanum species. Its various
biological activities were confirmed: antioxidant, anti-inflammatory, antibacterial, antifungal, anti-tumour, antinematodal,
and vasorelaxant action. Although vasodilation mediated by CRV was previously described, the exact mechanism of its action
has not yet been established. Hence, the aim of this study was to investigate CRV vasoactivity on human umbilical arteries (HUA)
and the different pathways involved in its mechanism of action using the tissue bath methodology. CRV caused a significant
decrease in vascular tension of 5-HT-pre-contracted umbilical arteries, with EC50 of 442.13 ± 33.8 μmol/L (mean ± standard error
of the mean——SEM). At 300 μmol/L, CRV shifted downward the 5-HT concentration–response curve with a statistical significance
of p < 0.001 obtained for the four highest concentrations. At a concentration of 1 mmol/L, CRV completely abolished BaCl2-
induced contraction in Ca2+-free Krebs–Ringer bicarbonate solution and the BAY K 8644-induced contraction in Krebs–Ringer
bicarbonate solution (p < 0.001). Isopentenyl pyrophosphate, the antagonist of TRPV3 channel, was able to decrease the efficacy
of CRV (p < 0.001). The blocking of L-type Ca2+ channels on smooth muscle cells is the most probable mechanism of CRV-induced
vasorelaxation. However, the role of TRPV3 channels in CRV-induced vasodilation of HUA cannot be excluded either.