Menthol relaxes rat aortae, mesenteric and coronary arteries by inhibiting calcium influx

Menthol, a naturally occurring compound in mint, is known to give cold sensation. However, previous findings about its pharmacological activity in blood vessels are full of paradox. The present study investigated the action of menthol on vascular reactivity in different arteries isolated from male Sprague-Dawley rats, e.g. aortae, main mesenteric arteries and coronary arteries. The arterial segments were suspended in organ bath or in wire myograph for measurement of isometric force. Menthol concentration-dependently relaxed all three arteries with similar relaxing sensitivity in arteries contracted by different contractors, KCl, U46619 (9,11-dideoxy-9α,11α-methanoepoxy Prostaglandin F_2α) and phenylephrine. Menthol-induced relaxations were unaffected by nitric oxide synthase inhibitor L-NAME, soluble guanylyl cyclase inhibitor ODQ, or mechanical removal of endothelium. Menthol also concentration-dependently suppressed 60 mM KCl-induced constriction and CaCl₂-induced contraction in Ca²⁺-free K ⁺-containing solution. Calcium fluorescent imaging using fluo-4 showed that 10 min-incubation with 1 mM menthol inhibited 60 mM KCl-induced Ca²⁺ influx in rat aortic smooth muscle cell line A7r5 and vascular smooth muscle of coronary arteries. To conclude, menthol induces relaxation and inhibits contraction in rat aortae, mesenteric and coronary arteries primarily through inhibiting Ca²⁺ influx via nifedipine-sensitive Ca ²⁺ channels in vascular smooth muscle.