Lack of role for nitric oxide in cholinergic modulation of myocardial contractility in vivo

2001 ◽  
Vol 281 (1) ◽  
pp. H198-H206 ◽  
Author(s):  
George J. Crystal ◽  
Xiping Zhou ◽  
Syed Alam ◽  
Agnieszka Piotrowski ◽  
Guochang Hu
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Vagal Stimulation ◽  
Negative Inotropic Effect ◽  
Cholinergic Modulation ◽  
No Donor ◽  
Flow Transducer ◽  
Before And After ◽  
Synthase Inhibitor

Despite intensive investigation, the role of nitric oxide (NO) in cholinergic modulation of myocardial contractility remains unresolved. The left anterior descending coronary artery of 34 anesthetized, open-chest dogs was perfused via an extracorporeal circuit. Segmental shortening (SS) was measured with ultrasonic crystals and coronary blood flow (CBF) was measured with an ultrasonic flow transducer. An intracoronary infusion of ACh (20 μg/min) was performed, with CBF held constant, under baseline and during dobutamine, CaCl2, or amrinone at doses increasing SS by ∼50% (10 μg/min, 15 mg/min, and 300 μg/min ic, respectively). ACh-induced responses during dobutamine were also assessed following treatment with the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME; 300 μg/min ic for 15 min). The effects of sodium nitroprusside (SNP; 80 μg/min ic), an exogenous NO donor, bradykinin (2.5 μg/min ic), a nonmuscarinic releaser of endothelial NO, and bilateral vagal stimulation (before and after l-NAME) were evaluated during dobutamine. ACh had no effect on SS under baseline or during CaCl2, but it decreased SS during dobutamine or amrinone (−23 ± 4% and −30 ± 5%, respectively). Vagal stimulation also reduced SS during dobutamine. l-NAME did not alter the ACh- or vagal-induced decreases in SS during dobutamine. Neither SNP nor bradykinin affected SS during dobutamine. In conclusion, ACh and vagal stimulation have a negative inotropic effect during stimulation of the β-adrenergic receptors that is independent of NO. The persistence of this effect during amrinone suggests that a mechanism downstream from adenylate cyclase is involved.

Nitric oxide does not modulate myocardial contractility acutely in in situ canine hearts

1996 ◽  
Vol 270 (5) ◽  
pp. H1568-H1576 ◽  
Author(s):  
G. J. Crystal ◽  
J. Gurevicius
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Oxygen Demand ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Local Concentration ◽  
Flow Transducer ◽  
Inotropic Effects ◽  
Arterial Blood

The study was designed to assess the influence of nitric oxide (NO) on myocardial contractility in vivo. The left anterior descending coronary artery (LAD) of 28 anesthetized, open-chest dogs was perfused with arterial blood via an extracorporeal circuit. In the LAD bed, segmental shortening (SS), an index of local myocardial contractility, was measured with ultrasonic crystals. Coronary blood flow (CBF) was measured by Doppler flow transducer and used to calculate myocardial oxygen consumption (MVO2). Studies were performed with coronary perfusion pressure (CPP) constant (n = 23) or with CBF constant (n = 5). Measurements were obtained 1) during intracoronary infusions of the NO donors sodium nitroprusside (SNP, 80 ng/min) and nitroglycerin (NTG, 40 micrograms/min) and of a stimulator of endogenous NO release, acetylcholine (ACh, 20 micrograms/min), and 2) after inhibition of basal NO synthase activity with either NG-nitro-L-arginine methyl ester (L-NAME, 300 micrograms/min ic for 15 min) or NG-monomethyl-L-arginine (L-NMMA 2mg/min ic for 15 min). Decreases in SS (-38%) and MVO2 (-42%) during intracoronary isoflurane infusion verified responsiveness of preparation to negative inotropic agents. With CPP constant, SNP, NTG, and ACh caused increases in CBF (177, 28, and 280%, respectively) with no changes in SS or MVO2. Neither L-NAME nor L-NMMA affected SS, MVO2, or CBF. With CBF constant, the SNP- and ACh-induced decreases in CPP were accompanied by no changes in SS. In conclusion, NO had no direct influence on myocardial contractility or oxygen demand under baseline conditions, or when its local concentration was increased acutely with SNP, NTG, or ACh. An augmented SS secondary to increased CBF per se, i.e., Gregg's phenomenon, did not obscure potential negative inotropic effects of SNP and ACh with CPP constant.

scholarly journals Nitric oxide inhibits basolateral 10-pS Cl− channels through the cGMP/PKG signaling pathway in the thick ascending limb of C57BL/6 mice

2016 ◽  
Vol 310 (8) ◽  
pp. F755-F762 ◽  
Author(s):  
Peng Wu ◽  
Zhongxiuzi Gao ◽  
Shiwei Ye ◽  
Zhi Qi
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylyl Cyclase ◽  
Inhibitory Effect ◽  
No Synthase ◽  
Thick Ascending Limb ◽  
Channel Activity ◽  
No Donor ◽  
Cgmp Analog ◽  
Synthase Inhibitor

We used patch-clamp techniques to examine whether nitric oxide (NO) decreases NaCl reabsorption by suppressing basolateral 10-pS Cl− channels in the thick ascending limb (TAL). Both the NO synthase substrate l-arginine (l-Arg) and the NO donor S-nitroso- N-acetylpenicillamine significantly inhibited 10-pS Cl− channel activity in the TAL. The inhibitory effect of l-Arg on Cl− channels was completely abolished in the presence of the NO synthase inhibitor or NO scavenger. Moreover, inhibition of soluble guanylyl cyclase abrogated the effect of l-Arg on Cl− channels, whereas the cGMP analog 8-bromo-cGMP (8-BrcGMP) mimicked the effect of l-Arg and significantly decreased 10-pS Cl− channel activity, indicating that NO inhibits basolateral Cl− channels by increasing cGMP production. Furthermore, treatment of the TAL with a PKG inhibitor blocked the effect of l-Arg and 8-BrcGMP on Cl− channels, respectively. In contrast, a phosphodiesterase 2 inhibitor had no significant effect on l-Arg or 8-BrcGMP-induced inhibition of Cl− channels. Therefore, we conclude that NO decreases basolateral 10-pS Cl− channel activity through a cGMP-dependent PKG pathway, which may contribute to the natriuretic and diuretic effects of NO in vivo.

Inhibition of nitric oxide synthase augments myocardial contractile responses to beta-adrenergic stimulation

1996 ◽  
Vol 271 (6) ◽  
pp. H2646-H2652 ◽  
Author(s):  
J. F. Keaney ◽  
J. M. Hare ◽  
J. L. Balligand ◽  
J. Loscalzo ◽  
T. W. Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Adrenergic Stimulation ◽  
Maximum Increase ◽  
Beta Adrenergic ◽  
Before And After ◽  
Nos Inhibitor ◽  
Oxide Synthase

Recent in vitro evidence suggests a role for nitric oxide (NO) in the modulation of myocardial contractility. The specific role of NO in the control of cardiac function in vivo, however, remains unclear. We investigated the effect of NO synthase (NOS) inhibition on myocardial contractility in response to beta-adrenergic stimulation in autonomically blocked dogs. Intracoronary infusions of dobutamine (1-50 micrograms/min) and isoproterenol (0.1 and 0.5 microgram/min) were performed before and after the intracoronary administration of the specific NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Intracoronary dobutamine resulted in a dose-dependent increase in peak first derivative of pressure (dP/dtmax) to a maximum of 195 +/- 10% (P < 0.001). After inhibition of NOS with intracoronary L-NAME at rates of 0.1 and 1 mg/min, the response to dobutamine was significantly enhanced with dP/dtmax, increasing 276 +/- 17 and 317 +/- 26%, respectively (P < 0.001). Intracoronary isoproterenol resulted in a maximum increase in dP/dtmax of 116 +/- 15% (P < 0.001) that further increased to 154 +/- 17 and 157 +/- 18% after NOS inhibition with 0.1 and 1 mg/min L-NAME, respectively (both P < 0.002). L-NAME had no effect on baseline dP/dtmax but did produce a reduction in myocardial guanosine 3',5'-cyclic monophosphate content. These results suggest a role for NO in the control of myocardial contractility in response to beta-adrenergic stimulation in vivo.

Role of nitric oxide and cAMP in prostaglandin-induced pial arterial vasodilation

1995 ◽  
Vol 268 (4) ◽  
pp. H1436-H1440 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Topical Administration ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Arterial Dilation ◽  
Synthase Inhibitor

The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to prostaglandin (PG)I2 and PGE2 in newborn pigs equipped with a closed cranial window. PGI2 (1–100 ng/ml) produced pial arterial dilation that was blunted by nitro-L-arginine (L-NNA, 10(-6) M), an NO synthase inhibitor (9 +/- 1 vs. 2 +/- 1%, 21 +/- 1 vs. 5 +/- 3% for 1 and 100 ng/ml PGI2 respectively, n = 6; means +/- SE). PGI2-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in cGMP were blocked by L-NNA (386 +/- 8 and 1,054 +/- 30 fmol/ml vs. 266 +/- 6 and 274 +/- 4 fmol/ml for control and PGI2 100 ng/ml before and after L-NNA respectively, n = 6). In contrast, PGI2-associated changes in CSF cAMP were unchanged by L-NNA (1,021 +/- 25 and 2,703 +/- 129 fmol/ml vs. 980 +/- 23 and 2,636 +/- 193 fmol/ml for control, PGI2 100 ng/ml before and after L-NNA, respectively, n = 6). PGE2 elicited similar changes in pial artery diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also being similarly inhibited by L-NNA. After L-NNA, topical administration of the NO donor sodium nitroprusside (SNP, 10(-9) M) increased pial artery diameter up to the resting level before L-NNA and partially restored the vasodilation elicited by PGI2 and PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide exerts feedback inhibition on EDHF-induced coronary arteriolar dilation in vivo

2000 ◽  
Vol 279 (2) ◽  
pp. H459-H465 ◽  
Author(s):  
Yasuhiro Nishikawa ◽  
David W. Stepp ◽  
William M. Chilian
Keyword(s):  
Nitric Oxide ◽  
Feedback Inhibition ◽  
Coronary Microcirculation ◽  
No Donor ◽  
Control Value ◽  
Before And After ◽  
Arteriolar Vasodilation ◽  
Dose Dependent ◽  
Cytochrome P 450

We tested the hypothesis that nitric oxide (NO) inhibits endothelium-derived hyperpolarizing factor (EDHF)-induced vasodilation via a negative feedback pathway in the coronary microcirculation. Coronary microvascular diameters were measured using stroboscopic fluorescence microangiography. Bradykinin (BK)-induced dilation was mediated by EDHF, when NO and prostaglandin syntheses were inhibited, or by NO when EDHF and prostaglandin syntheses were blocked. Specifically, BK (20, 50, and 100 ng · kg−1 · min−1 ic) caused dose-dependent vasodilation similarly before and after administration of N G-monomethyl-l-arginine (l-NMMA) (3 μmol/min ic for 10 min) and indomethacin (Indo, 10 mg/kg iv). The residual dilation to BK withl-NMMA and Indo was completely abolished by suffusion of miconazole or an isosmotic buffer containing high KCl (60 mM), suggesting that this arteriolar vasodilation is mediated by the cytochrome P-450 derivative EDHF. BK-induced dilation was reduced by 39% after inhibition of EDHF and prostaglandin synthesis, and dilation was further inhibited by combined blockade withl-NMMA to a 74% reduction in the response. This suggests an involvement for NO in the vasodilation. After dilation to BK was assessed with l-NMMA and Indo, sodium nitroprusside (SNP, 1–3 μg · kg−1 · min−1ic), an exogenous NO donor, was administered in a dose to increase the diameter to the original control value. Dilation to BK was virtually abolished when administered concomitantly with SNP duringl-NMMA and Indo ( P < 0.01 vs. before SNP), suggesting that NO inhibits EDHF-induced dilation. SNP did not affect adenosine- or papaverine-induced arteriolar dilation in the presence ofl-NMMA and Indo, demonstrating that the effect of SNP was not nonspecific. In conclusion, our data are the first in vivo evidence to suggest that NO inhibits the production and/or action of EDHF in the coronary microcirculation.

Abstract 18060: TRAIL Promotes Angiogenesis and Ischemia-Induced Neovascularisation via NOX4, H2O2 and Nitric Oxide-Dependent Mechanisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Belinda A Di Bartolo ◽  
Sian P Cartland ◽  
Leonel Prado-Lourenco ◽  
Nor Saadah M Azahri ◽  
Thuan Thai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiogenic Factor ◽  
Tubule Formation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Therapeutic Implications ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
First Time

Background: Angiogenesis and neovascularization are essential processes that follow ischemia insults. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only induces endothelial cell (EC) death and inhibits angiogenesis, but also promotes EC migration, invasion and proliferation in vitro . These seemingly opposite effects make its role in angiogenesis in vivo unclear. Using TRAIL -/- and wild-type mice, we sought to determine the role of TRAIL in angiogenesis and neovascularisation. We also sought mechanisms in vitro . Methods and Results: Reduced vascularisation assessed by real-time in vivo 3D Vevo ultrasound imaging and CD31 staining was observed in TRAIL -/- mice 28 d after hindlimb ischemia. Moreover, reduced capillary formation and increased apoptosis was evident in TRAIL -/- muscles even at 3 d after ischemic surgery. We have previously shown that fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, regulates TRAIL gene expression in vascular smooth muscle cells. Indeed, FGF-2 also regulates TRAIL expression in ECs, and FGF-2-inducible proliferation, migration and tubule formation was inhibited with siRNA targeting TRAIL. Notably, both FGF-2 and TRAIL significantly increased NOX4 expression. TRAIL-inducible angiogenic activity in ECs was inhibited with siRNAs targeting NOX4, and consistent with these, NOX4 mRNA was reduced in 3 d ischemic hindlimbs of TRAIL -/- mice. TRAIL stimulated intracellular H 2 O 2 levels in ECs, and TRAIL-inducible proliferation, migration and tubule formation was inhibited with not only PEG-catalase, a H 2 O 2 scavenger, but also blocked with L-NAME, a nitric oxide synthase inhibitor. Conclusions: This is the first demonstration showing that TRAIL promotes angiogenesis in vivo . We show for the first time that the TRAIL stimulates NOX4 expression to mediate nitric oxide-dependent angiogenic effects. This has significant therapeutic implications such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with CVD and diabetes.

Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle

2007 ◽  
Vol 293 (4) ◽  
pp. E1062-E1068 ◽  
Author(s):  
Vitor A. Lira ◽  
Quinlyn A. Soltow ◽  
Jodi H. D. Long ◽  
Jenna L. Betters ◽  
Jeff E. Sellman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Glucose Transporter ◽  
No Donor ◽  
Ampk Signaling ◽  
L6 Myotubes ◽  
Glut4 Expression ◽  
Compound C ◽  
Cgmp Analog

Nitric oxide (NO) and 5′-AMP-activated protein kinase (AMPK) are involved in glucose transport and mitochondrial biogenesis in skeletal muscle. Here, we examined whether NO regulates the expression of the major glucose transporter in muscle (GLUT4) and whether it influences AMPK-induced upregulation of GLUT4. At low levels, the NO donor S-nitroso- N-penicillamine (SNAP, 1 and 10 μM) significantly increased GLUT4 mRNA (∼3-fold; P < 0.05) in L6 myotubes, and cotreatment with the AMPK inhibitor compound C ablated this effect. The cGMP analog 8-bromo-cGMP (8-Br-cGMP, 2 mM) increased GLUT4 mRNA by ∼50% ( P < 0.05). GLUT4 protein expression was elevated 40% by 2 days treatment with 8-Br-cGMP, whereas 6 days treatment with 10 μM SNAP increased GLUT4 expression by 65%. Cotreatment of cultures with the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one prevented the SNAP-induced increase in GLUT4 protein. SNAP (10 μM) also induced significant phosphorylation of α-AMPK and acetyl-CoA carboxylase and translocation of phosphorylated α-AMPK to the nucleus. Furthermore, L6 myotubes exposed to 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) for 16 h presented an approximately ninefold increase in GLUT4 mRNA, whereas cotreatment with the non-isoform-specific NOS inhibitor NG-nitro-l-arginine methyl ester, prevented ∼70% of this effect. In vivo, GLUT4 mRNA was increased 1.8-fold in the rat plantaris muscle 12 h after AICAR injection, and this induction was reduced by ∼50% in animals cotreated with the neuronal and inducible nitric oxide synthases selective inhibitor 1-(2-trifluoromethyl-phenyl)-imidazole. We conclude that, in skeletal muscle, NO increases GLUT4 expression via a cGMP- and AMPK-dependent mechanism. The data are consistent with a role for NO in the regulation of AMPK, possibly via control of cellular activity of AMPK kinases and/or AMPK phosphatases.

Effects of Hypoxic Acclimation, Muscle Strain and Contraction Frequency on Nitric Oxide-Mediated Myocardial Performance in Steelhead Trout (Oncorhynchus mykiss)

2021 ◽  
Author(s):  
Christian Carnevale ◽  
Douglas A. Syme ◽  
A. Kurt Gamperl
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Soluble Guanylyl Cyclase ◽  
Surprising Result ◽  
Muscle Strain ◽  
No Donor ◽  
Contraction Frequency ◽  
Mediated Effects ◽  
Oxide Synthase ◽  
Hypoxic Acclimation

Whether hypoxic acclimation influences nitric oxide (NO)-mediated control of fish cardiac function is not known. Thus, we measured the function / performance of myocardial strips from normoxia and hypoxia-acclimated (40% air saturation; ~ 8 kPa O2) trout at several frequencies (20 - 80 contractions min-1) and two muscle strain amplitudes (8 and 14%) when exposed to increasing concentrations of the NO donor sodium nitroprusside (SNP) (10-9 to 10-4 M). Further, we examined the influence of: 1) nitric oxide synthase (NOS) produced NO (by blocking NOS with 10-4 M L-NMMA); and 2) soluble guanylyl cyclase mediated, NOS-independent, NO effects (i.e., after blockade with 10-4 M ODQ), on myocardial contractility. Hypoxic acclimation increased twitch duration by 8-10% and decreased mass-specific net power by ~35%. However, hypoxic acclimation only had minor impacts on the effects of SNP and the two blockers on myocardial function. The most surprising result of this study was the degree to which contraction frequency and strain amplitude influenced NO-mediated effects on myocardial power. For example, at 8% strain 10-4 SNP resulted in a decrease in net power of ~30% at 20 min-1 but an increase of ~20% at 80 min-1, and this effect was magnified at 14% strain. This study: suggests that hypoxic acclimation has only minor effects on NO-mediated myocardial contractility in salmonids; is the first to report the highly frequency- and strain-dependent nature of NO effects on myocardial contractility in fishes; and supports previous work showing that NO effects on the heart (myocardium) are finely tuned spatio-temporally.

Abstract 16720: Cytoglobin Regulates Cardiovascular Function and Vessel Tone by Controlling the Rate of Vascular Nitric Oxide Metabolism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xiaoping Liu ◽  
Mohamed A El-Mahdy ◽  
Raed S Ismail ◽  
Sean Little ◽  
Le T Thuy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Wall ◽  
No Donor ◽  
Nitric Oxide Metabolism ◽  
No Consumption ◽  
Potent Vasodilator ◽  
Inner Diameter ◽  
The Difference ◽  
Synthase Inhibitor

Cytoglobin (Cygb) can effectively metabolize nitric oxide (NO), a potent vasodilator, in the presence of oxygen and reductants. Cygb in the vascular wall may affect cardiovascular functions by changing the rate of NO metabolism. In this study, we directly tested the vascular role of Cygb using Cygb knockout (Cygb-/-) mice. The mean blood pressure of Cygb-/- and C57BL/6 wild type (WT) mice was 65.3 ± 1.9 mmHg and 93.7 ± 1.5 mmHg, respectively (n=10). Using echocardiography, we observed that cardiac output (CO) was increased in Cygb-/- mice compared to WT with values of 29.8 ± 3.9 vs 17.7 ± 0.9 ml/min. The systemic vascular resistance (SVR) of Cygb-/- mice was decreased by ~60% vs that of WT mice (Fig. 1). Further, the inner diameter (id) of aorta of Cygb-/- mice was dilated compared to WT with values of 2.2 ± 0.1 mm vs 1.5 ± 0.05 mm (n=5), respectively. After treatment with the NO synthase inhibitor L-NAME, no difference in the aortic id remained between Cygb-/- (1.55 ± 0.03 mm) and WT (1.49 ± 0.02 mm) mice, indicating that the NO pathway is responsible for the difference in vascular inner diameters and tone. Myograph experiments show that the aortic vasodilation response of Cygb-/- mice is much more sensitive to acetylcholine (Ach) or the NO donor nitroprusside (SNP) (EC50 shifts from 13 nM and 2.9 nM (WT mice) to 0.33 nM and 0.16 nM (Cygb-/-) for Ach and SNP, respectively). Using NO electrodes to measure the rate of NO consumption by SMCs and quantitative imunoblotting to estimate Cygb content in RSMCs-AR and Cygb knockdown RSMCs, we observed that 90% of NO consumption by RSMCs-AR is caused by the intracellular Cygb. Our results indicate that Cygb deficiency in the vascular wall of Cygb-/- mice greatly reduces the rate of NO metabolism and increases vascular NO concentration, resulting in vasodilation, increase in vessel lumen diameter, and decrease in SVR. These results demonstrate that Cygb regulates cardiac function and vessel tone by controlling the rate of vascular NO metabolism.

Role of nitric oxide in gut ischemia-reperfusion-induced hepatic microvascular dysfunction

1997 ◽  
Vol 273 (5) ◽  
pp. G1007-G1013 ◽  
Author(s):  
Yoshinori Horie ◽  
Robert Wolf ◽  
D. Neil Granger
Keyword(s):  
Nitric Oxide ◽  
Important Determinant ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
Protective Action ◽  
Microvascular Dysfunction ◽  
Artery Occlusion ◽  
No Donor ◽  
Synthase Inhibitor

The overall objective of this study was to assess the contribution of an altered bioavailability of nitric oxide (NO) to the leukocyte adhesion and hypoxic stress elicited in the liver by gut ischemia-reperfusion (I/R). The accumulation of leukocytes, number of nonperfused sinusoids (NPS), and NADH autofluorescence were monitored (by intravital microscopy) in mouse liver after 15 min of superior mesenteric artery occlusion and 60 min of reperfusion. Leukostasis, NPS, and NADH autofluorescence (indicating hypoxia) were all increased in the liver at 60 min after gut I/R. The NO synthase inhibitor N G-monomethyl-l-arginine (l-NMMA) exaggerated the liver leukostasis elicited by gut I/R, responses that were prevented by coadministration of l-arginine. The NO donor diethylenetriamine-NO (DETA-NO) andl-arginine were both effective in attenuating the gut I/R-induced leukostasis and increased NADH autofluorescence, whereas neither DETA nord-arginine exerted a protective action. These findings indicate that NO is an important determinant of the liver leukostasis, impaired sinusoidal perfusion, and tissue hypoxia elicited by gut I/R.

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