High Blood Pressure Upregulates Arterial L-Type Ca2+ Channels Is Membrane Depolarization the Signal?

Long-lasting Ca (CaL) channels of the Cav1.2 gene family contribute to the pathogenesis of abnormal arterial tone in hypertension. The physiological stimulus that enhances CaL channel current in the vascular smooth muscle cells (VSMCs) remains unknown. The present study investigated if high blood pressure triggers an upregulation of vascular CaL channel protein. Rat aortae were banded between the origins of the left renal (LR) and right renal (RR) arteries to selectively elevate blood pressure in the proximal RR arteries. After 2 days, the immunoreactivity on Western blots corresponding to the pore-forming α1C subunit of the CaL channel was increased 3.25-fold in RR compared with LR arteries. This finding persisted at 28 days and was associated with abnormal Ca-dependent tone and higher CaL currents in the VSMCs exposed to high pressure. Based on microelectrode studies indicating that RR arteries were depolarized compared with LR arteries, further studies examined if membrane depolarization, an inherent response of VSMCs to high blood pressure, increased α1C expression. Isolated rat renal arteries were cultured for 2 days in low K (4 mmol/L) or depolarizing high K (30 mmol/L) media. Arteries preconditioned in high K showed a 5.47-fold increase in α1C expression, enhanced CaL channel current, and elevated Ca-dependent tone. These findings provide the first direct evidence that high blood pressure upregulates the CaL channel α1C subunit in VSMCs in vivo and suggest that membrane depolarization is a potential signal involved in this interaction that may contribute to the development of abnormal vascular tone.