Carvacrol inhibits TRPM7‐like current in native myocytes from mesenteric artery of Hypertensive Rats

Abstract

Carvacrol, a phenolic monoterpene, is found in several plants of Origanum genus and has been described to cause vasodilatation in mesenteric artery from normotensive rats by reducing Ca2+ influx in vascular smooth muscle cells (VSMC). Then, the aim of this study was to investigate the effect of carvacrol on TRPM6/TRPM7 channels in VSMC from normotensive and hypertensive rats. Under whole‐cell voltage‐clamp, with voltage‐dependent Ca2+ and K+ channels blocked, currents generated by TRPM6/TRPM7 channels were measured by symmetrical voltage ramp commands to potentials between −100 to +100 mV, from a holding potential of 0 mV, displaying outward rectification in physiological extracellular medium. In VSMC isolated from hypertensive rats, carvacrol (100 and 300 μM) inhibit significantly both inward (−80 mV) and outward (+80 mV) currents [(current values at − 80 mV: (−3.42 ± 0.47 pA/pF; N = 5, control); (−1.07 ± 0.07 pA/pF, N = 5, p<0.05, carvacrol 100 μM); (−1.86 ± 0.34 pA/pF, N = 5, p<0.05, carvacrol 300 μM); (current values at + 80 mV: −6.21 ± 0.57 pA/pF, N = 5, control); (−3.53 ± 0.28 pA/pF, N = 5, p<0.01, carvacrol 100 μM); (−2.29 ± 0.27 pA/pF, N = 5, p<0.001, carvacrol 300 μM)]. This effect was similar to that induced by elevating extracellular Mg2+ (2.5 mM, N=5). In the presence of 2‐APB (100 μM, N=5), a TRPM7 blocker, no additional effect in TRPM7/TRPM6 whole‐cell current was observed after perfusion with carvacrol (300 μM; N=5), suggesting that probably, the effect of carvacrol is through inhibition of TRPM7‐like currents (ITRPM7) in VSMC. Additionally, since the sensitivity of TRPM7 channels to Mg2+ is an essential condition, we examined whether the above described current is inhibited by high concentrations of intracellular Mg2+. In this condition, the magnitude of TRPM7‐like current was significantly decreased inward and outward currents, in both myocytes, from hypertensive and normotensive rats, confirming that ITRPM were ITRPM6/TRPM7. In conclusion, these data demonstrate that carvacrol inhibited ITRPM6/TRPM7, in myocytes isolated from mesenteric artery of hypertensive and normotensive rats. This study provides the first electrophysiological evidence of TRPM7‐like current in native VSMC from mesenteric artery.Support or Funding InformationFundação de Amparo à pesquisa do estado da Bahia (FAPESB) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).