Cyclic GMP-independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor

We previously observed that endothelin-1 (ET-1)-induced gastric vasoconstriction is enhanced after ischemia-reperfusion. The purpose of our present study was to examine the role of nitric oxide in regulating ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion. Using a mechanically perfused stomach segment from chloralose-anesthetized dogs, we examined 1) responses to NG-nitro-L-arginine methyl ester (L-NAME) alone and in combination with L-arginine, 2) whether L-NAME affects ET-1-induced vasoconstriction under normal conditions and after ischemia-reperfusion, and 3) if spermine NONOate inverted question mark1,3-propanediamine-N-[4-1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazi no] butyl; a nitric oxide donor inverted question mark attenuates the augmented response to ET-1 after ischemia-reperfusion. Our results show that 1) L-NAME significantly increased baseline vascular resistance and this response was reduced by L-arginine, 2) ET-1-induced vasoconstriction was enhanced by L-NAME, and 3) administration of spermine NONOate during reperfusion largely attenuated the vasoconstrictor response to ET-1 after ischemia-reperfusion. Our findings are consistent with the hypothesis that nitric oxide modulates responses to ET-1 under normal conditions, and loss of this vasodilator after ischemia-reperfusion results in an augmented response to ET-1.

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Evidence that nitric oxide synthase is involved in progesterone-induced acrosomal exocytosis in mouse spermatozoa

Reproduction Fertility and Development ◽

10.1071/r96044 ◽

1997 ◽

Vol 9 (4) ◽

pp. 433 ◽

Cited By ~ 30

Author(s):

María Beléen Herrero ◽

J. Marcelo Viggiano ◽

Silvina Pérez Martínez ◽

Martha F. de Gimeno

Keyword(s):

Nitric Oxide ◽

Methyl Ester ◽

Nitric Oxide Synthase ◽

No Synthase ◽

Nitric Oxide Donor ◽

Mouse Sperm ◽

Acrosomal Exocytosis ◽

Oxide Synthase ◽

Spermine Nonoate

In a recent work, we detected nitric oxide synthase (NO synthase) in the acrosome and tail of mouse and human spermatozoa by an immunofluorescence technique. Also, NO-synthase inhibitors added during sperm capacitationin vitro reduced the percentage of oocytes fertilized in vitro, suggesting a role for NO synthase in sperm function. Therefore, in the present study the effect of three NO-synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-D-arginine methyl ester (D-NAME) and L-NG-nitro-arginine (NO2-arg), and of a nitric oxide donor, spermine-NONOate, on the progesterone-induced acrosome reaction of mouse sperm was examined. NO-synthase inhibitors were added at 0, 60 or 90 min during capacitation; at 120 min, mouse epididymal spermatozoa were exposed to 15 µM progesterone for another 15 min. In another set of experiments, different concentrations of spermine-NONOate were added to capacitated spermatozoa for 15 min; in these experiments, progesterone was not included. NO2-arg and L-NAME blocked progesterone-induced exocytosis regardless of the time at which these inhibitors were added. Moreover, D-NAME did not inhibit exocytosis. In contrast, spermine-NONOate stimulated the acrosomal exocytosis in vitro directly. These results provide evidence that mouse sperm NO synthase participates in the progesterone-induced acrosome reactionin vitro and that nitric oxide induces this event.

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Endothelium-derived NO, but not cyclic GMP, is required for hypoxic augmentation in isolated porcine coronary arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00258.2011 ◽

2011 ◽

Vol 301 (6) ◽

pp. H2313-H2321 ◽

Cited By ~ 29

Author(s):

Calvin K. Y. Chan ◽

Judith Mak ◽

Yuansheung Gao ◽

Ricky Y. K. Man ◽

Paul M. Vanhoutte

Keyword(s):

Nitric Oxide ◽

Protein Kinase ◽

Coronary Arteries ◽

Cyclic Gmp ◽

Guanylyl Cyclase ◽

Calcium Influx ◽

Soluble Guanylyl Cyclase ◽

Isometric Tension ◽

Nitric Oxide Donor ◽

Atpase Inhibitor

The present study investigated the mechanism underlying the transient potentiation of vasoconstriction by hypoxia in isolated porcine coronary arteries. Isometric tension was measured in rings with or without endothelium. Hypoxia (Po2 <30 mmHg) caused a transient further increase in tension (hypoxic augmentation) in contracted (with U46619) preparations. The hypoxic response was endothelium dependent and abolished by inhibitors of nitric oxide synthase [ Nω-nitro-l-arginine methyl ester (l-NAME)] or soluble guanylyl cyclase (ODQ and NS2028). The addition of DETA NONOate (nitric oxide donor) in the presence of l-NAME restored the hypoxic augmentation, suggesting the involvement of the nitric oxide pathway. However, the same was not observed after incubation with 8-bromo-cyclic GMP, atrial natriuretic peptide, or isoproterenol. Assay of the cyclic GMP content showed no change upon exposure to hypoxia in preparations with and without endothelium. Incubation with protein kinase G and protein kinase A inhibitors did not inhibit the hypoxic augmentation. Thus the hypoxic augmentation is dependent on nitric oxide and soluble guanylyl cyclase but independent of cyclic GMP. The hypoxic augmentation persisted in calcium-free buffer and in the presence of nifedipine, ruling out a role for extracellular calcium influx. Hypoxia did not alter the intracellular calcium concentration, as measured by confocal fluorescence microscopy. This observation and the findings that hypoxic augmentation is enhanced by thapsigargin (sarco/endoplasmic reticulum calcium ATPase inhibitor) and inhibited by HA1077 or Y27632 (Rho kinase inhibitors) demonstrate the involvement of calcium sensitization in the phenomenon.

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Guanylyl cyclase stimulatory coupling to KCachannels

AJP Cell Physiology ◽

10.1152/ajpcell.2000.279.6.c1938 ◽

2000 ◽

Vol 279 (6) ◽

pp. C1938-C1945 ◽

Cited By ~ 36

Author(s):

M. Nara ◽

P. D. K. Dhulipala ◽

G. J. Ji ◽

U. R. Kamasani ◽

Y.-X. Wang ◽

...

Keyword(s):

Nitric Oxide ◽

Protein Kinase ◽

Guanylyl Cyclase ◽

Phosphorylation Site ◽

Nitric Oxide Donor ◽

Dependent Manner ◽

Dependent Protein Kinase ◽

Α Subunit ◽

Dependent Protein ◽

Spermine Nonoate

We coexpressed the human large-conductance, calcium-activated K (KCa) channel (α- and β-subunits) and rat atrial natriuretic peptide (ANP) receptor genes in Xenopus oocytes to examine the mechanism of guanylyl cyclase stimulatory coupling to the channel. Exposure of oocytes to ANP stimulated whole cell KCa currents by 21 ± 3% (at 60 mV), without altering current kinetics. Similarly, spermine NONOate, a nitric oxide donor, increased KCa currents (20 ± 4% at 60 mV) in oocytes expressing the channel subunits alone. Stimulation of KCacurrents by ANP was inhibited in a concentration-dependent manner by a peptide inhibitor of cGMP-dependent protein kinase (PKG). Receptor/channel stimulatory coupling was not completely abolished by mutating the cAMP-dependent protein kinase phosphorylation site on the α-subunit (S869; Nars M, Dhulipals PD, Wang YX, and Kotlikoff MI. J Biol Chem 273: 14920–14924, 1998) or by mutating a neighboring consensus PKG site (S855), but mutation of both residues virtually abolished coupling. Spermine NONOate also failed to stimulate channels expressed from the double mutant cRNAs. These data indicate that nitric oxide donors stimulate KCa channels through cGMP-dependent phosphorylation and that two serine residues (855 and 869) underlie this stimulatory coupling.

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Nitric Oxide Donor NOR 3 Inhibits Ketogenesis from Oleate in Isolated Rat Hepatocytes by a Cyclic GMP-Independent Mechanism

Pharmacology & Toxicology ◽

10.1111/j.1600-0773.1998.tb01396.x ◽

1998 ◽

Vol 82 (1) ◽

pp. 40-46 ◽

Cited By ~ 5

Author(s):

Takahide Nomura ◽

Masatsugu Ohtsuki ◽

Shigeru Matsui ◽

Chiho Sumi-Ichinose ◽

Hiroko Nomura ◽

...

Keyword(s):

Nitric Oxide ◽

Cyclic Gmp ◽

Rat Hepatocytes ◽

Nitric Oxide Donor ◽

Isolated Rat Hepatocytes ◽

Independent Mechanism ◽

Isolated Rat

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The Nitric Oxide Donor SIN-1 Protects Endothelial Cells from Tumor Necrosis Factor- -Mediated Cytotoxicity: Possible Role For Cyclic GMP and Heme Oxygenase

Journal of Molecular and Cellular Cardiology ◽

10.1006/jmcc.1997.0565 ◽

1997 ◽

Vol 29 (12) ◽

pp. 3305-3310 ◽

Cited By ~ 20

Author(s):

Tobias Polte ◽

Stefanie Oberle ◽

Henning Schröder

Keyword(s):

Nitric Oxide ◽

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Heme Oxygenase ◽

Cyclic Gmp ◽

Tumor Necrosis ◽

Nitric Oxide Donor ◽

Necrosis Factor

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Heme oxygenase-1 induction depletes heme and attenuates pulmonary artery relaxation and guanylate cyclase activation by nitric oxide

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00846.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. H1244-H1250 ◽

Cited By ~ 12

Author(s):

Christopher J. Mingone ◽

Mansoor Ahmad ◽

Sachin A. Gupte ◽

Joseph L. Chow ◽

Michael S. Wolin

Keyword(s):

Nitric Oxide ◽

Pulmonary Artery ◽

Organ Culture ◽

Heme Oxygenase ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Pulmonary Arteries ◽

Heme Oxygenase 1 ◽

No Donor ◽

Spermine Nonoate

This study examines in endothelium-denuded bovine pulmonary arteries the effects of increasing heme oxygenase-1 (HO-1) activity on relaxation and soluble guanylate cyclase (sGC) activation by nitric oxide (NO). A 24-h organ culture with 0.1 mM cobalt chloride (CoCl2) or 30 μM Co-protoporphyrin IX was developed as a method of increasing HO-1 expression. These treatments increased HO-1 expression and HO activity by approximately two- to fourfold and lowered heme levels by 40–45%. Induction of HO-1 was associated with an attenuation of pulmonary arterial relaxation to the NO-donor spermine-NONOate. The presence of a HO-1 inhibitor 30 μM chromium mesoporphyrin during the 24-h organ culture (but not acute treatment with this agent) reversed the attenuation of relaxation to NO seen in arteries co-cultured with agents that increased HO-1. Relaxation to isoproterenol, which is thought to be mediated through cAMP, was not altered in arteries with increased HO-1. Inducers of HO-1 did not appear to alter basal sGC activity in arterial homogenates or expression of the β1-subunit of sGC. However, the increase in activity seen in the presence of 1 μM spermine-NONOate was attenuated in homogenates obtained from arteries with increased HO-1. Since arteries with increased HO-1 had decreased levels of superoxide detected by the chemiluminescence of 5 μM lucigenin, superoxide did not appear to be mediating the attenuation of relaxation to NO. These data suggest that increasing HO-1 activity depletes heme, and this is associated with an attenuation of pulmonary artery relaxation and sGC activation responses to NO.

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