Effects of hydrogen sulphide in smooth muscle

• Published in: Pharmacology & therapeutics (Oxford) 2016-02, Vol.158, p.101-113
• Main Authors: Dunn, William R, Alexander, Stephen P H, Ralevic, Vera, Roberts, Richard E
• Format: Article
• Language: English
• Subjects: Animals; Humans; Hydrogen Sulfide - pharmacology; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth - drug effects; Myocytes, Smooth Muscle - drug effects; Vasoconstriction - drug effects; Vasodilation - drug effects
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2015.12.007

In recent years, it has become apparent that the gaseous pollutant, hydrogen sulphide (H2S) can be synthesised in the body and has a multitude of biological actions. This review summarizes some of the actions of this 'gasotransmitter' in influencing the smooth muscle that is responsible for controlling muscular activity of hollow organs. In the vasculature, while H2S can cause vasoconstriction by complex interactions with other biologically important gases, such as nitric oxide, the prevailing response is vasorelaxation. While most vasorelaxation responses occur by a direct action of H2S on smooth muscle cells, it has recently been proposed to be an endothelium-derived hyperpolarizing factor. H2S also promotes relaxation in other smooth muscle preparations including bronchioles, the bladder, gastrointestinal tract and myometrium, opening up the opportunity of exploiting the pharmacology of H2S in the treatment of conditions where smooth muscle tone is excessive. The original concept, that H2S caused smooth muscle relaxation by activating ATP-sensitive K(+) channels, has been supplemented with observations that H2S can also modify the activity of other potassium channels, intracellular pH, phosphodiesterase activity and transient receptor potential channels on sensory nerves. While the enzymes responsible for generating endogenous H2S are widely expressed in smooth muscle preparations, it is much less clear what the physiological role of H2S is in determining smooth muscle contractility. Clarification of this requires the development of potent and selective inhibitors of H2S-generating enzymes.