TRPM8 downregulation by angiotensin II in vascular smooth muscle cells is involved in hypertension.

Abstract

Angiotensin II (AngII)-induced injury of vascular smooth muscle cells (VSMCs) serves an important role in hypertension and other cardiovascular disorders. Transient receptor potential melastatin8 (TRPM8) is a thermally‑regulated Ca2+‑permeable channel that is activated by reduced body temperature. Although several recent studies have revealed the regulatory effect of TRPM8 in vascular tone and hypertension, the precise role of TRPM8 in dysfunction of vascular smooth muscle cells (VSMCs) induced by AngII remains elusive. In the present study, the possible function of TRPM8 in AngII‑induced VSMCs malfunction invivo and invitro was investigated. In the aortae from rats that had undergone a two‑kidney one‑clip operation, which is a widely‑used renovascular hypertension model, the mRNA and protein levels of TRPM8 were reduced. In addition, exogenous AngII treatment decreased TRPM8 mRNA and protein expression levels in primary cultures of rat VSMCs. TRPM8 activation by menthol, a pharmacological agonist, in VSMCs, significantly attenuated the AngII‑induced increase in reactive oxygen species and H2O2 production. In addition, TRPM8 activation reduced the AngII‑induced upregulation of NADPH oxidase (NOX)1 and NOX4 in VSMCs. Furthermore, TRPM8 activation relieved the AngII‑induced activation of ras homolog gene family, member A‑rho associated protein kinase2 and janus kinase2 signaling pathways in VSMCs. In conclusion, the results presented in the current study indicated that TRPM8 downregulation by AngII in VSMCs may be involved in hypertension.