Acute and chronic effects of nitric oxide on cardiomyocyte guanylyl cyclase : implications for the modulation of the heart following environmental, physiological and clinical exposure to nitric oxide
type: CreativeWork
description: The nitric oxide (NO) - guanylyl cyclase (GC) - guanosine 3' ,5'-cyclic monophosphate (cGMP) signal transduction pathway has been shown to play a role in the modulation of ventricular contractility by the parasympathetic nervous system. Environmental/occupational NO exposures, the gastric production of NO from ingested nitrites, organic nitrate vasodilator therapy and sepsis are situations in which the body tissues are exposed to elevated levels of NO. This may in turn disrupt signal transduction through this pathway. NO-GC coupling in adult rat ventricular cardiomyocytes was investigated in this study following exposure of the cardiomyocytes to a "NO-rich" environment using two different experimental protocols: (i) ' in vitro' exposure of cardiomyocytes to NO-donors for short (2 hr) and long (24 hr) durations and (ii) injection of rats with bacterial endotoxin (LPS) to create a septic condition. GC activity was determined in cytosolic fractions of the cardiomyocytes and also in 'intact' cardiomyocytes following permeabilization with digitonin. Cardiomyocytes were shown to possess NO-sensitive GC which was localized in the cytosol. GC activity in the absence of added NO (basal activity) was low but was powerfully stimulated by nitroprusside (NP) and S-nitroso-d,l-acetylpenicillamine (SNAP). NO-stimulated GC was inhibited by physiologically relevant concentrations of free Ca2+. Furthermore, NO-stimulated GC in the cardiomyocytes was relatively insensitive to the NO-stimulated GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In vitro exposure of cardiomyocytes to SNAP and NP was found to have dramatic effects on the properties of GC. Following treatment of the cardiomyocytes with SNAP, but not NP, basal GC activity was significantly increased. The activated state was long lived and was still present following processing of the cardiomyocytes to obtain a cytosolic fraction. The activation of GC did not result from the uptake of SNAP into the cardiomyocyt…
abstract: The nitric oxide (NO) - guanylyl cyclase (GC) - guanosine 3' ,5'-cyclic monophosphate (cGMP) signal transduction pathway has been shown to play a role in the modulation of ventricular contractility by the parasympathetic nervous system. Environmental/occupational NO exposures, the gastric production of NO from ingested nitrites, organic nitrate vasodilator therapy and sepsis are situations in which the body tissues are exposed to elevated levels of NO. This may in turn disrupt signal transduction through this pathway. NO-GC coupling in adult rat ventricular cardiomyocytes was investigated in this study following exposure of the cardiomyocytes to a "NO-rich" environment using two different experimental protocols: (i) ' in vitro' exposure of cardiomyocytes to NO-donors for short (2 hr) and long (24 hr) durations and (ii) injection of rats with bacterial endotoxin (LPS) to create a septic condition. GC activity was determined in cytosolic fractions of the cardiomyocytes and also in 'intact' cardiomyocytes following permeabilization with digitonin. Cardiomyocytes were shown to possess NO-sensitive GC which was localized in the cytosol. GC activity in the absence of added NO (basal activity) was low but was powerfully stimulated by nitroprusside (NP) and S-nitroso-d,l-acetylpenicillamine (SNAP). NO-stimulated GC was inhibited by physiologically relevant concentrations of free Ca2+. Furthermore, NO-stimulated GC in the cardiomyocytes was relatively insensitive to the NO-stimulated GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In vitro exposure of cardiomyocytes to SNAP and NP was found to have dramatic effects on the properties of GC. Following treatment of the cardiomyocytes with SNAP, but not NP, basal GC activity was significantly increased. The activated state was long lived and was still present following processing of the cardiomyocytes to obtain a cytosolic fraction. The activation of GC did not result from the uptake of SNAP into the cardiomyocyt…
author: Davis, John Paul
language: en_US
date published: 1999-01-01
date modified: 2026-07-24T04:26:59Z
provider: University of Saskatchewan
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Saskatchewan

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property ID: Handle
value: https://hdl.handle.net/10388/etd-10212004-001208