Transient Receptor Potential Vanilloid Type 1 Receptors in Hypertensive Renal Damage: A Promising Therapeutic Target?

摘要

In the development and progression of hypertensive organ damage, hemodynamic factors such as high pressure, turbulent flow, and shear stress are thought to cause endothelial dysfunction and vascular remodeling. Nephrosclerosis may eventually result from a complex cascade of inflammatory and fibrotic processes. Research on novel therapeutic targets has, therefore, focused on regulatory systems that play a significant role for the regulation of blood pressure and volume homeostasis,as well as for modulating inflammation or fibrosis. The autonomic innervation of the kidney may be such a regulatory system but has been difficult to study at the molecular level.This issue of Hypertension contains a report by Wang et al that is an important step forward in that regard. The authors studied the transient receptor potential vanilloid type 1 (TRPV1) receptor, a member of the mammalian transient receptor potential channel superfamily. Transient receptor potential channels mediate the transmembrane flux of cations down their electrochemical gradients, thereby raising intracellular Ca~(2+) and Na~+ concentrations and depolarizing the cell. The TRPV1 channel was identified by expression cloning using the hot pepper- derived vallinoid compound capsaicin as a ligand and is, therefore, referred to as the capsaicin or vallinoid receptor. TRPV1 channels are mainly expressed on a subset of primary afferent neurons, with unmyelinated (C-fibers) or thinly myelinated axons (Adelta-fibers). TRFV1 channels are not only sensitive to capsaicin but can be stimulated by thermal, acidic, chemical, or mechanical factors, as well as endogenous arachidonic acid derivates, such as anandamide.