Transient receptor potential channels in essential hypertension

Abstract

OBJECTIVE: The role of nonselective cation channels of the transient receptor potential channel (TRPC) family in essential hypertension has not yet been investigated. METHODS: We studied TRPCs in 51 patients with essential hypertension and 51 age-matched and sex-matched normotensive control subjects. Calcium and gadolinium influx into human monocytes was determined using the fluorescent dye technique. TRPC expression was measured using reverse transcriptase-polymerase chain reaction and in-cell western assay. Gene silencing by small interfering RNA for specific TRPC knockdown was also performed. RESULTS: We observed an increased gadolinium/calcium-influx ratio through TRPC in essential hypertensive patients compared with normotensive control subjects [cation influx ratio (mean +/- SEM), 125 +/- 14 versus 80 +/- 7%; each n = 51; P < 0.01], due to an increase of gadolinium influx in hypertensive patients compared with normotensive control subjects (48 +/- 4 versus 36 +/- 3%; each n = 51; P < 0.05). We observed a significant increase of TRPC3 and TRPC5 protein expression in essential hypertensive patients compared with normotensive control subjects (normalized TRPC3 expression, 3.21 +/- 0.59 versus 1.36 +/- 0.07; each n = 20; P < 0.01; normalized TRPC5 expression, 2.10 +/- 0.28 versus 1.40 +/- 0.52; each n = 12; P < 0.05). We used small interfering RNA for knockdown of TRPC5. The thereby reduced channel expression caused a significant attenuation of calcium and gadolinium influx. CONCLUSION: This study points to an important role of TRPCs in essential hypertension.