Investigation of terpinen-4-ol effects on vascular smooth muscle relaxation.

AIMS: This study investigated the mechanisms underlying the vascular effects of terpinen-4-ol in isolated rat aortic ring preparations. MAIN METHODS: The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. KEY FINDINGS: Terpinen-4-ol reversibly relaxed endothelium-containing preparations pre-contracted with high K(+) and phenylephrine with IC50 values of 421.43 µM and 802.50 µM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca(2+)-free and high K(+) (80 mM) medium, the contractions produced by Ba(2+) were reduced by terpinen-4-ol (100-1000 µM) in a concentration-dependent manner. In aortic rings maintained under Ca(2+)-free conditions, terpinen-4-ol significantly reduced the contractions induced by either phenylephrine (1 µM) or phorbol 12,13-dibutyrate (1 µM). Terpinen-4-ol (10-1000 µM) also relaxed the contractions evoked by BAYK-8644 (3 µM) with an IC50 of 454.23 µM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by terpinen-4-ol exposure. SIGNIFICANCE: The present results suggest that terpinen-4-ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through voltage-operated calcium channels.

Carvacrol decreases neuronal excitability by inhibition of voltage-gated sodium channels.

The monoterpenoid carvacrol (1) is present in many essential oils of plants and has attracted attention because of its beneficial biological activities, especially analgesic activity. However, the mechanism of action of 1 remains unknown. The present study aimed to explore the mechanisms whereby 1 produces its effects on the peripheral nervous system. Carvacrol reversibly blocked the excitability of the rat sciatic nerve in a concentration-dependent manner with an IC(50) value of 0.50 ± 0.04 mM. At 0.6 mM, 1 increased the rheobase from 3.30 ± 0.06 V to 4.16 ± 0.14 V and the chronaxy from 59.6 ± 1.22 µs to 75.0 ± 1.82 µs. Also, 1 blocked the generation of action potentials (IC(50) 0.36 ± 0.14 mM) of the intact dorsal root ganglion (DRG) neurons without altering the resting potential and input resistance. Carvacrol reduced the voltage-gated sodium current of dissociated DRG neurons (IC(50) 0.37 ± 0.05 mM). In this study it has been demonstrated that 1 blocks neuronal excitability by a direct inhibition of the voltage-gated sodium current, which suggests that this compound acts as a local anesthetic. The present findings add valuable information to help understand the mechanisms implicated in the analgesic activity of carvacrol.