Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications

The heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for nitric oxide (NO). sGC is a heterodimeric enzyme with α and β subunits and contains a heme moiety essential for binding of NO and activation of the enzyme. Stimulation of sGC mediates physiologic responses including sm...

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Main Authors: Bobby Nossaman, Edward Pankey, Philip Kadowitz
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Critical Care Research and Practice
Online Access:http://dx.doi.org/10.1155/2012/290805
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author Bobby Nossaman
Edward Pankey
Philip Kadowitz
author_facet Bobby Nossaman
Edward Pankey
Philip Kadowitz
author_sort Bobby Nossaman
collection DOAJ
description The heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for nitric oxide (NO). sGC is a heterodimeric enzyme with α and β 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.
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spelling doaj-art-4825c561049b499086863990ace708892025-02-03T06:07:10ZengWileyCritical Care Research and Practice2090-13052090-13132012-01-01201210.1155/2012/290805290805Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic IndicationsBobby Nossaman0Edward Pankey1Philip Kadowitz2Critical Care Medicine Section, Department of Anesthesiology, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121, USADepartment of Pharmacology, SL83, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USADepartment of Pharmacology, SL83, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112-2699, USAThe heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for nitric oxide (NO). sGC is a heterodimeric enzyme with α and β 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.http://dx.doi.org/10.1155/2012/290805
spellingShingle Bobby Nossaman
Edward Pankey
Philip Kadowitz
Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
Critical Care Research and Practice
title Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
title_full Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
title_fullStr Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
title_full_unstemmed Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
title_short Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications
title_sort stimulators and activators of soluble guanylate cyclase review and potential therapeutic indications
url http://dx.doi.org/10.1155/2012/290805
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