Pathophysiological implications of transient receptor potential channels in vascular function.

PURPOSE OF REVIEW: Although Ca influx plays a pivotal role in neurohormonal and myogenic control of vascular tone and slow progressive vascular remodeling, the molecular identification of those Ca sources/pathways had long been elusive. The review will introduce recent discoveries that mammalian homologues of Drosophila transient receptor potential protein expressed in various regions of the vasculature exhibit appropriate features to elucidate these pathways, with associated dysfunctions. RECENT
FINDINGS: Recent investigations have revealed that expressed as well as native vascular transient receptor potentials behave as Ca-permeable cation channels that open in response to phospholipase C-coupled vasoconstrictors, mechanical forces and/or hypertrophic stimuli, thereby regulating the vascular resistance/tone and blood pressure/flow, and proliferative/apoptotic reorganization of vascular tissues. Notably, one vascular function relies on the coordinated interplay of multiple vascular transient receptor potential isoforms and vice versa. Imbalance of expression and altered activities of these vascular isoforms likely contribute to disorders such as hypertension, vasospasm, atherosclerosis and aneurysm.
SUMMARY: Such multifunctionality and multifaceted aspects of vascular transient receptor potentials not only suggest their unprecedented importance in regulating vascular functions, but may also offer the possibility of developing new drugs or 'calcium antagonists' that would work more selectively and elaborately for a wide range of vascular diseases based on entirely different strategies.