TY - JOUR TI - Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure AU - MacKay, Charles E AU - Leo, M Dennis AU - Fernández-Peña, Carlos AU - Hasan, Raquibul AU - Yin, Wen AU - Mata-Daboin, Alejandro AU - Bulley, Simon AU - Gammons, Jesse AU - Mancarella, Salvatore AU - Jaggar, Jonathan H A2 - Nelson, Mark T A2 - Aldrich, Richard W VL - 9 PY - 2020 DA - 2020/05/04 SP - e56655 C1 - eLife 2020;9:e56655 DO - 10.7554/eLife.56655 UR - https://doi.org/10.7554/eLife.56655 AB - PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature. KW - flow mediated-vasodilation KW - polycystin-2 KW - blood pressure KW - endothelial cell JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -