Brief topical application of TRPV3 channel agonist carvacrol mediates skin vasodilation via NOS, COX, and K+ channel pathways in young adults

We investigated the influence of a brief, 1-min topical application of carvacrol, a transient receptor potential vanilloid 3 (TRPV3) channel activator, on cutaneous vasodilation and the mechanism(s) governing this response. In experiment 1 (n = 10), cutaneous vascular conductance (CVC) was measured for 90 min at four forearm sites treated with: 1) lactated Ringer's serving as a control, 2) 20 mM L-NAME, a nitric oxide synthase (NOS) inhibitor, 3) 10 mM ketorolac, a cyclooxygenase (COX) inhibitor, or 4) both inhibitors combined. In experiment 2 (n = 10), CVC was assessed at four forearm sites for 90 min treated with: 1) lactated Ringer's, 2) 50 mM tetraethylammonium, a Ca²⁺-activated K⁺ (KCa) channel blocker, 3) 10 mM 4-Aminopyridine, a voltage-gated K⁺ (Kv) channel blocker, and 4) 50 mM BaCl₂, a non-selective K⁺ channel blocker. 10 % carvacrol was topically applied for 1 min at all sites using a cotton swab, with inhibitors/blockers administered intradermally via microdialysis. At the control site, carvacrol elevated CVC to ∼40 %max, a response that persisted throughout 90 min. This increase was attenuated by separate and combined inhibition of NOS and COX (≥30 min), as well as by KCa channel blockade (20-50 min) and non-selective K⁺ channel blockade (from 20 min onward). Kv blockade augmented carvacrol-induced increases in CVC during early stage (10-20 min). We showed that a brief, 1-min topical activation of TRPV3 channels with 10 % carvacrol induced a moderate and prolonged cutaneous vasodilation in young adults, mediated through NOS-, COX-, and K⁺-channel dependent pathways.