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.
Subject(s)
Hypertension/metabolism , Monocytes/metabolism , Transient Receptor Potential Channels/metabolism , Aged , Calcium/metabolism , Case-Control Studies , Cations/metabolism , Female , Gadolinium/metabolism , Humans , Male , Middle Aged , RNA Interference , RNA, Small Interfering , TRPC Cation Channels/metabolismABSTRACT
Intermittent hemodynamic instability during hemodialysis treatment is a frequent complication in patients with end-stage renal failure. A noninvasive method for continuous hemodynamic monitoring is needed. We used noninvasive digital photoplethysmography and an algorithm for continuous, investigator-independent, automatic analysis of digital volume pulse in 10 healthy subjects and in 20 patients with end-stage renal failure during the hemodialysis session. The reflective index was defined representing the diastolic component of the digital pulse wave. The properties of the reflective index were studied in healthy control subjects (n=10). An increased reflective index was due to increased peripheral pulse wave reflection (e.g., vasoconstriction). During a hemodialysis session, the reflective index increased significantly from 36+/-3 arbitrary units to 41+/-3 arbitrary units (n=20; p<0.05) measured using digital photoplethysmography. This increase appeared in 15 of the 20 patients with end-stage renal failure. Our data establish digital photoplethysmography as a noninvasive, reliable, and sensitive method for continuous monitoring during the hemodialysis session.
