Eugenol Dilates Rat Cerebral Arteries by Inhibiting Smooth Muscle Cell Voltage-dependent Calcium Channels

Abstract

Plants high in eugenol, a phenylpropanoid compound, are used as folk medicines to alleviate diseases including hypertension. Eugenol has been demonstrated to relax conduit and ear arteries and reduce systemic blood pressure, but mechanisms involved are unclear. Here, we studied eugenol regulation of resistance-size cerebral arteries that control regional brain blood pressure and flow and investigated mechanisms involved. We demonstrate that eugenol dilates arteries constricted by either pressure or membrane depolarization (60 mM K+) in a concentration-dependent manner. Experiments performed using patch-clamp electrophysiology demonstrated that eugenol inhibited voltage-dependent calcium (Ca2+) currents, when using Ba2+ as a charge carrier, in isolated cerebral artery smooth muscle cells. Eugenol inhibition of voltage-dependent Ca2+ currents involved pore block, a hyperpolarizing shift ( ~−10 mV) in voltage-dependent inactivation, an increase in the proportion of steady-state inactivating current, and acceleration of inactivaiton rate. In summary, our data indicate that eugenol dilates cerebral arteries via multi-modal inhibition of voltage-dependent Ca2+ channels.

Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels

“…Eugenol also relaxed endothelium-denuded arteries. One explanation for this effect is that eugenol blocks voltagedependent Ca 2+ channels in arterial smooth muscle cells to induce vasodilatation (Peixoto-Neves et al, 2014). In the present study, HC-067047, a selective TRPV4 channel blocker, attenuated eugenol-induced relaxation in endotheliumdenuded arteries, suggesting that TRPV4 channels in cells other than endothelial cells are involved in this response.…”

“…Our results indicate an EC50 for eugenol of ∼48 μM in small mesenteric arteries. In rat endotheliumintact cerebral arteries and aorta, eugenol induced relaxation with EC50s of ∼235 and ∼140 μM respectively (Damiani et al, 2003;Peixoto-Neves et al, 2014). In tracheal smooth muscle, the eugenol EC50 was ∼570 μM (Lima et al, 2011).…”

Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis

“…These data might reflect that eugenol pretreatment could effectively reduce myocardial injury after heart transplantation. The mechanism behind this outcome might be related to the anti-inflammatory and anti-oxidative stress effects of eugenol as reported by other studies ( 14 , 15 , 17 ). Myocardial ischemia and hypoxia can increase the expression of inflammatory cytokine IL-6 ( 29 , 30 ) and subsequently activate various immune-related receptors to release TNF-α from cardiac mast cells, macrophages and endothelial cells ( 31 , 32 ).…”

Cardiovascular Activity of the Chemical Constituents of Essential Oils

“…This effect was probably mediated by the antioxidant proprieties of this compound. Peixoto-Neves et al [ 63 ] showed that Eugenol promoted a concentration-dependent dilation of the cerebral arteries by an inhibition of Calcium voltage-dependent channel, which was confirmed by patch-clamp studies.…”