scholarly journals Stimulation of soluble guanylate cyclase by superoxide dismutase is mediated by NO

1998 ◽  
Vol 335 (3) ◽  
pp. 527-531 ◽  
Author(s):  
Andreas FRIEBE ◽  
Günter SCHULTZ ◽  
Doris KOESLING
Keyword(s):  
Superoxide Dismutase ◽  
Xanthine Oxidase ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Hydroxyl Radical Scavengers ◽  
Fold Activation ◽  
Messenger Molecule ◽  
Generating System ◽  
Intercellular Messenger ◽  
Stimulation Of

Soluble guanylate cyclase (sGC), which is found in many cells and tissues, represents the receptor for the intra- and intercellular messenger molecule NO. Superoxide dismutase (SOD), an enzyme involved in the degradation of toxic superoxide radicals, has been proposed as a non-NO activator of sGC. Here we show that SOD stimulated sGC purified from bovine lung up to 10-fold. Activation by SOD was not influenced by the hydroxyl radical scavengers mannitol and DMSO. In contrast, the presence of the NO scavengers oxyhaemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, as well as the O2--generating system xanthine oxidase/hypoxanthine, led to inhibition of SOD-stimulated cGMP production. NO-insensitive sGC mutants were not influenced either by SOD or by xanthine oxidase. We have previously shown that sGC was stimulated by NO present in the normal atmosphere. Here we show that the SOD effect depended on the NO concentration from the atmosphere, as the stimulation of sGC by defined NO gases (0, 120, 330 and 1000 parts per billion NO) was potentiated by SOD. NO stimulation of sGC and its potentiation by SOD were inhibited by oxyhaemoglobin to identical levels. We conclude that the SOD-mediated stimulation of sGC is due to the elimination of superoxide, thereby preventing its reaction with NO to form peroxynitrite.

Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low-renin and high-renin models

2010 ◽  
Vol 28 (8) ◽  
pp. 1666-1675 ◽  
Author(s):  
Yuliya Sharkovska ◽  
Philipp Kalk ◽  
Bettina Lawrenz ◽  
Michael Godes ◽  
Linda Sarah Hoffmann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Organ Damage ◽  
Stimulation Of

scholarly journals Acute stimulation of the soluble guanylate cyclase does not impact on left ventricular capacitance in normal and hypertrophied porcine hearts in vivo

2018 ◽  
Vol 315 (3) ◽  
pp. H669-H680 ◽  
Author(s):  
Alessio Alogna ◽  
Michael Schwarzl ◽  
Martin Manninger ◽  
Nazha Hamdani ◽  
Birgit Zirngast ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Diastolic Pressure ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Concentric Hypertrophy ◽  
Ventricular Compliance ◽  
Left Ventricular Compliance ◽  
Stimulation Of

Experimental data indicate that stimulation of the nitric oxide-soluble guanylate cyclase(sGC)-cGMP-PKG pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy Landrace pigs and 7 pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume relationships (EDPVRs) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 μg·kg−1·min−1 for 30 min, respectively). Separately, in seven healthy and six DOCA pigs, transmural LV biopsies were harvested from the beating heart to measure titin phosphorylation during BAY 41-8543 infusion. LV EDPVRs before and during BAY 41-8543 infusion were superimposable in both healthy and DOCA-treated pigs, whereas mean aortic pressure decreased by 20–30 mmHg in both groups. Myocardial titin phosphorylation was unchanged in healthy pigs, but total and site-specific (Pro-Glu-Val-Lys and N2-Bus domains) titin phosphorylation was increased in DOCA-treated pigs. Bicoronary nitroglycerin infusion in healthy pigs ( n = 5) induced a rightward shift of the LV EDPVR, demonstrating the responsiveness of the pathway in this model. Acute systemic sGC stimulation with the sGC stimulator BAY 41-8543 did not recruit an LV preload reserve in both healthy and hypertrophied LV porcine myocardium, although it increased titin phosphorylation in the latter group. Thus, increased titin phosphorylation is not indicative of increased in vivo LV capacitance. NEW & NOTEWORTHY We demonstrate that acute pharmacological stimulation of soluble guanylate cyclase does not increase left ventricular compliance in normal and hypertrophied porcine hearts. Effects of long-term soluble guanylate cyclase stimulation with oral compounds in disease conditions associated with lowered myocardial cGMP levels, i.e., heart failure with preserved ejection fraction, remain to be investigated.

Activation of endothelin ETB receptors increases glomerular cGMP via an L-arginine-dependent pathway

1992 ◽  
Vol 263 (6) ◽  
pp. F1020-F1025 ◽  
Author(s):  
R. M. Edwards ◽  
M. Pullen ◽  
P. Nambi
Keyword(s):  
Nitric Oxide ◽  
Guanylate Cyclase ◽  
Binding Sites ◽  
Soluble Guanylate Cyclase ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
High Affinity ◽  
Dependent Pathway ◽  
Stimulation Of

The effects of endothelins (ET) on guanosine 3',5'-cyclic monophosphate (cGMP) levels in intact rat glomeruli were examined. ET-3 produced a rapid approximately fivefold increase in cGMP levels with the maximum effect occurring at 1 min. The ET-3-induced increase in cGMP accumulation occurred in the absence and presence of 3-isobutyl-1-methylxanthine. ET-1, ET-2, ET-3, and the structurally related toxin, sarafotoxin S6c, all increased glomerular cGMP levels in a concentration-dependent manner and with similar potencies (EC50 approximately 15-30 nM). The L-arginine analogue, N omega-nitro-L-arginine (L-NNA), reduced basal levels of cGMP and also totally inhibited ET-induced increases in cGMP as did methylene blue, an inhibitor of soluble guanylate cyclase. The effect of L-NNA was attenuated by L-arginine but not by D-arginine. The stimulation of cGMP accumulation by ET-3 was dependent on extracellular Ca2+ and was additive to atriopeptin III but not to acetylcholine. The ETA-selective antagonist, BQ 123, had no effect on ET-3-induced formation of cGMP. Glomerular membranes displayed high-affinity (Kd = 130-150 pM) and high-density (approximately 2.0 pmol/mg) binding sites for 125I-ET-1 and 125I-ET-3. ET-1, ET-3, and sarafotoxin S6c displaced 125I-ET-1 binding to glomerular membranes with similar affinities. BQ 123 had no effect on 125I-ET-1 binding. We conclude that ET increases cGMP levels in glomeruli by stimulating the formation of a nitric oxide-like factor that activates soluble guanylate cyclase. This effect of ET appears to be mediated by activation of ETB receptors and may serve to modulate the contractile effects of ET.

scholarly journals Hemolysis and iodination of erythrocyte components by a myeloperoxidase- mediated system

Blood ◽  
1975 ◽  
Vol 45 (5) ◽  
pp. 699-707 ◽  
Author(s):  
SJ Klebanoff ◽  
RA Clark
Keyword(s):  
Superoxide Dismutase ◽  
Thyroid Hormones ◽  
Glucose Oxidase ◽  
Xanthine Oxidase ◽  
Combined Effect ◽  
Oxidase System ◽  
Generating System

Abstract Erythrocytes are hemolyzed by myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase; hypoxanthine + xanthine oxidase) and an oxidizable cofactor (chloride, iodide, thyroxine, triiodothyronine). The combined effect of chloride and either iodide or the thyroid hormones is greater than additive. Myeloperoxidase can be replaced by lactoperoxidase in the iodide-, thyroxine and triiodothyronine- dependent, but not in the chloride-dependent, systems. Hemolysis is is inhibited by the peroxidase inhibitors, azide and cyanide, and by catalase and is stimulated by superoxide dismutase when the xanthine oxidase system is employed as the source of H2O2. Hemolysis by the iodide-dependent system is associated with the iodination of erythrocyte components.

Thiol-independent stimulation of soluble guanylate cyclase by NO-containing compounds

1991 ◽  
Vol 41 (11) ◽  
pp. 1777-1779 ◽  
Author(s):  
Feraydoon Niroomand ◽  
Alexander Mülsch ◽  
Eycke Böhme
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Stimulation Of

scholarly journals Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced chronic glomerulosclerosis

2005 ◽  
Vol 68 (1) ◽  
pp. 47-61 ◽  
Author(s):  
Yingrui Wang ◽  
Stephanie Kramer ◽  
Tanja Loof ◽  
Sebastian Martini ◽  
Susanne Kron ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Stimulation Of

scholarly journals Stimulation of soluble guanylate cyclase accelerates renal recovery following relief of unilateral ureteral obstruction

2009 ◽  
Vol 9 (S1) ◽  
Author(s):  
Yingrui Wang-Rosenke ◽  
Dmytro Khadzhynov ◽  
Tanja Loof ◽  
Stephanie Krämer ◽  
Bogdan Iliev ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Ureteral Obstruction ◽  
Soluble Guanylate Cyclase ◽  
Unilateral Ureteral Obstruction ◽  
Renal Recovery ◽  
Stimulation Of

scholarly journals Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

2009 ◽  
Vol 32 (7) ◽  
pp. 597-603 ◽  
Author(s):  
Hiroyuki Masuyama ◽  
Toshihiro Tsuruda ◽  
Yoko Sekita ◽  
Kinta Hatakeyama ◽  
Takuroh Imamura ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Rat Heart ◽  
Soluble Guanylate Cyclase ◽  
Pharmacological Stimulation ◽  
Pressure Independent ◽  
Independent Effects ◽  
Stimulation Of
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