Expression levels of TRPC1 and TRPC6 ion channels are reciprocally altered in aging rat aorta: implications for age-related vasospastic disorders

摘要

We previously showed that the expression of transient receptor potential canonical (TRPC)6 ion channel elevated when TRPC1 was knocked down in A7r5 cultured vascular smooth muscle cells. Therefore, the purpose of this study was to explore whether TRPC6 is also upregulated in aging rat aorta comparable to that of TRPC1 in longitudinal in vivo aging model. We further investigated a possible causal relationship between altered phenylephrine-induced contractions and the expression levels of TRPC6, a purported essential component of alpha-adrenergic receptor signaling in aging aorta. Immunoblot analysis showed that TRPC1 protein levels significantly decreased whereas TRPC6 increased drastically in aorta from 16- to 20-month-old rats compared to that from 2 to 4 months. Immunohistochemical data demonstrated spatial changes in TRPC6 expression within the smooth muscle layers along with increased detection in the adventitia of the aged rat aorta. The phenylephrine-induced contractions were potentiated in aging aorta. In conclusion, based on this aging model, TRPC6 overexpression could be related with TRPC1 downregulation and might be responsible for the increased adrenoceptor sensitivity which contributes to the development of age-related vasospastic disorders.