抄録
Vascular functions are regulated not only by chemical mediators,such as hormones, cytokines, and neurotransmitters, but by shear stress, a mechanical force generated by blood flow. The endothelial cells that line blood vessels recognize shear stress, and transmit the signal into the interior of the cell, where it triggers cell responses that involve changes in cell morphology, cell function, and gene expression. Ca2+signaling plays an important role in shear-stress signal transduction. Our previous studies demonstrated that a shear-stress-dependent Ca2+ influx occurs in endothelial cells when exposed to flow, and that an ATP-operated cation channel, P2X4, is the major contributor to flow-induced Ca2+ influx. The flow-induced activation of P2X4 requires ATP, which is supplied by the endogenous ATP released by endothelial cells. Cell surface ATP synthase localized in lipid rafts in the endothelial cell membrane is involved in ATP release in response to shear stress. To gain insight into the physiological significance of this shear-stress signal transduction via P2X4, we generated a P2X4-deficient mouse, which does not exhibit normal endothelial cell responses to flow, such as Ca2+ influx and subsequent production of nitric oxide (NO), a potent vasodilator. The vasodilation induced by an acute increase in blood flow in situ is markedly suppressed in P2X4--deficient mice, and they have higher blood pressure values and excrete smaller amounts of NO products in their urine than wild-type mice. Thus, endothelial P2X4 channels are critical to the flow (shear-stress)-sensitive mechanism that regulates vascular functions. [J Physiol Sci. 2007;57 Suppl:S28]
