Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
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- Bobby Nossaman
- Critical Care Medicine Section, Department of Anesthesiology, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USA
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- Edward Pankey
- Department of Pharmacology, SL83, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA
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- Philip Kadowitz
- Department of Pharmacology, SL83, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USA
説明
<jats:p>The heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for nitric oxide (NO). sGC is a heterodimeric enzyme with<jats:italic>α</jats:italic>and<jats:italic>β</jats:italic>subunits and contains a heme moiety essential for binding of NO and activation of the enzyme. Stimulation of sGC mediates physiologic responses including smooth muscle relaxation, inhibition of inflammation, and thrombosis. In pathophysiologic states, NO formation and bioavailability can be impaired by oxidative stress and that tolerance to NO donors develops with continuous use. Two classes of compounds have been developed that can directly activate sGC and increase cGMP formation in pathophysiologic conditions when NO formation and bioavailability are impaired or when NO tolerance has developed. In this report, we review current information on the pharmacology of heme-dependent stimulators and heme-independent activators of sGC in animal and in early clinical studies and the potential role these compounds may have in the management of cardiovascular disease.</jats:p>
収録刊行物
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- Critical Care Research and Practice
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Critical Care Research and Practice 2012 1-12, 2012
Hindawi Limited