Regulation of cardiovascular TRP channel functions along the NO–cGMP–PKG axis

Abstract

There is growing body of evidence that nitric oxide (NO)–cGMP–PKG signaling plays a central role in negative regulation of cardiovascular (CV) responses and its disorders through suppressed Ca²⁺ dynamics. Other lines of evidence also reveal the stimulatory effects of this signaling on some CV functions. Recently, transient receptor potential (TRP) channels have received much attention as non-voltage-gated Ca²⁺ channels involved in CV physiology and pathophysiology. Available information suggests that these channels undergo both inhibition and activation by NO via PKG-mediated phosphorylation and S-nitrosylation, respectively, and also act as upstream regulators to promote endothelial NO production. This review summarizes the roles of NO–cGMP–PKG signaling pathway, particularly in regulating TRP channel functions with their associated physiology and pathophysiology.

Keywords::

• angiogenesis
• cardiac hypertrophy
• cardiomyopathy
• vascular permeability
• vascular proliferative disease
• vascular tone regulation

Financial & competing interests disclosure

This work is supported in part by grants-in-aid to Ryuji Inoue from the Japan Society for the Promotion of Science, Tokyo Biochemical Research Foundation and Vehicle Racing Commemorative Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.