Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure

2005 ◽  
Vol 288 (5) ◽  
pp. H2332-H2341 ◽  
Author(s):  
Hong Zheng ◽  
Yi-Fan Li ◽  
Kurt G. Cornish ◽  
Irving H. Zucker ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Exercise Training ◽  
Paraventricular Nucleus ◽  
No Donor ◽  
Protein Levels ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Dose Dependent

Previously, we have demonstrated that an altered endogenous nitric oxide (NO) mechanism within the paraventricular nucleus (PVN) contributes to increased renal sympathetic nerve activity (RSNA) in heart failure (HF) rats. The goal of this study was to examine the effect of exercise training (ExT) in improving the endogenous NO mechanism within the PVN involved in the regulation of RSNA in rats with HF. ExT significantly restored the decreased number of neuronal NO synthase (nNOS)-positive neurons in the PVN (129 ± 17 vs. 99 ± 6). nNOS mRNA expression and protein levels in the PVN were also significantly increased in HF-ExT rats compared with HF-sedentary rats. To examine the functional role of NO within the PVN, an inhibitor of NOS, NG-monomethyl-l-arginine, was microinjected into the PVN. Dose-dependent increases in RSNA, arterial blood pressure (BP), and heart rate (HR) were produced in all rats. There was a blunted increase in these parameters in HF rats compared with the sham-operated rats. ExT significantly augmented RSNA responses in rats with HF (33% vs. 20% at the highest dose), thus normalizing the responses. The NO donor sodium nitroprusside, microinjected into the PVN, produced dose-dependent decreases in RSNA, BP, and HR in both sham and HF rats. ExT significantly improved the blunted decrease in RSNA in HF rats (36% vs. 17% at the highest dose). In conclusion, our data indicate that ExT improves the altered NO mechanism within the PVN and restores NO-mediated changes in RSNA in rats with HF.

Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice

2000 ◽  
Vol 278 (5) ◽  
pp. H1679-H1685 ◽  
Author(s):  
Katalin Kauser ◽  
Valdeci da Cunha ◽  
Richard Fitch ◽  
Cornell Mallari ◽  
Gabor M. Rubanyi
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Apolipoprotein E ◽  
Lesion Size ◽  
Significant Inhibition ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Progression Of Atherosclerosis ◽  
Apoe Ko

This study investigated the role of endogenous nitric oxide (NO) in the progression of atherosclerosis in apolipoprotein E-deficient [apoE-knockout (KO)] mice. Mice were treated with N ω-nitro-l-arginine methyl ester (l-NAME) an inhibitor of nitric oxide synthase (NOS) or with the NOS substrate l-arginine for 8 wk.l-NAME treatment resulted in a significant inhibition of NO-mediated vascular responses and a significant increase in the atherosclerotic plaque/surface area in the aorta of apoE-KO mice.l-arginine treatment had no influence on endothelial function and did not alter lesion size. Mean arterial blood pressure and serum lipid levels were not altered by the treatments. At the beginning of the study impairment in endothelial function was only apparent in the case of N G-nitro-l-arginine-induced, NO-mediated contraction, whereas ACh-induced, NO-mediated relaxation was not different between age-matched apoE-KO and C57Bl/6J mice. After the 8-wk treatment with the NOS inhibitor, both NO-mediated responses were significantly inhibited. The acceleration in lesion size concomitant to the severely impaired NO-mediated responses indicates that lack of endogenous NO is an important progression factor of atherosclerosis in the apoE-KO mouse.

scholarly journals Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function

2014 ◽  
Vol 306 (5) ◽  
pp. H690-H698 ◽  
Author(s):  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
Clark T. Holdsworth ◽  
Scott K. Ferguson ◽  
Danielle J. McCullough ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Citrate Synthase ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Metabolic Demand ◽  
No Donor ◽  
Microvascular Oxygenation

Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2 mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO2 mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 ± 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min; −14% grade downhill running) groups. PO2 mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP; NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts ( p < 0.05 for both). The overall speed of the PO2 mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 ± 1.4, trained: 32.3 ± 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 ± 1.5, trained: 31.0 ± 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 ± 6.8, trained: 55.5 ± 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO2 mv kinetics) following contractions onset in rats with CHF.

scholarly journals Exercise training and muscle microvascular oxygenation: functional role of nitric oxide

2012 ◽  
Vol 113 (4) ◽  
pp. 557-565 ◽  
Author(s):  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
Scott K. Ferguson ◽  
Clark T. Holdsworth ◽  
Danielle J. McCullough ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Peak Oxygen Uptake ◽  
Sprague Dawley ◽  
No Donor ◽  
Phosphorescence Quenching ◽  
Metabolic Adaptations ◽  
Sprague Dawley Rats ◽  
Microvascular Oxygenation

Exercise training induces multiple adaptations within skeletal muscle that may improve local O2delivery-utilization matching (i.e., Po2mv). We tested the hypothesis that increased nitric oxide (NO) function is intrinsic to improved muscle Po2mv kinetics from rest to contractions after exercise training. Healthy young Sprague-Dawley rats were assigned to sedentary ( n = 18) or progressive treadmill exercise training ( n = 10; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min, −14% grade) groups. Po2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP, NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (l-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained rats had greater peak oxygen uptake (V̇o2peak) than their sedentary counterparts (81 ± 1 vs. 72 ± 2 ml·kg−1·min−1, respectively; P < 0.05). Exercise-trained rats had significantly slower Po2mv fall throughout contractions (τ1; time constant for the first component) during control (sedentary: 8.1 ± 0.6; trained: 15.2 ± 2.8 s). Compared with control, SNP slowed τ1to a greater extent in sedentary rats (sedentary: 38.7 ± 5.6; trained: 26.8 ± 4.1 s; P > 0.05) whereas l-NAME abolished the differences in τ1between sedentary and trained rats (sedentary: 12.0 ± 1.7; trained: 11.2 ± 1.4 s; P < 0.05). Our results indicate that endurance exercise training leads to greater muscle microvascular oxygenation across the metabolic transient following the onset of contractions (i.e., slower Po2mv kinetics) partly via increased NO-mediated function, which likely constitutes an important mechanism for training-induced metabolic adaptations.

scholarly journals Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin

1997 ◽  
Vol 82 (3) ◽  
pp. 913-917 ◽  
Author(s):  
Lance S. Terada ◽  
John E. Repine ◽  
Dale Piermattei ◽  
Brooks M. Hybertson
Keyword(s):  
Nitric Oxide ◽  
Xanthine Oxidase ◽  
Surface Expression ◽  
No Donor ◽  
Endogenous Nitric Oxide ◽  
Inflammatory Processes ◽  
The Media ◽  
Neutrophil Adherence ◽  
Synthase Inhibitor

Terada, Lance S., John E. Repine, Dale Piermattei, and Brooks M. Hybertson. Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin. J. Appl. Physiol. 82(3): 913–917, 1997.—The oxygen radical-producing enzyme xanthine oxidase (XO) can promote neutrophil adherence to endothelium. Recognizing that a balance often exists in inflammatory processes, we sought to determine whether XO initiates antiadherent pathways. We found that bovine pulmonary arterial endothelial cells (EC) exposed to XO released increased amounts of nitrite into the media, reflecting an increased production of nitric oxide (NO). When EC were subjected to shear stress, treatment with XO and/or the NO synthase inhibitor Nω-nitro-l-arginine (l-NNA) increased neutrophil rolling behavior and firm neutrophil adherence to EC in an additive fashion. Both rolling and adherent interactions were abolished by monoclonal antibodies directed against P-selectin. In addition, treatment of EC with XO and/orl-NNA increased both surface expression of P-selectin and release of von Willebrand factor into media. Finally, treatment of EC with the NO donor sodium nitroprusside decreased XO-mediated neutrophil rolling and adherence. We conclude that XO stimulates EC to produce NO and that NO decreases the P-selectin-dependent neutrophil adhesion initiated by XO. Such increases in endogenous NO may constitute an important negative-feedback response to the acute proadhesive effects of XO.

Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure

2007 ◽  
Vol 292 (1) ◽  
pp. H149-H157 ◽  
Author(s):  
Maram K. Reddy ◽  
Harold D. Schultz ◽  
Hong Zheng ◽  
Kaushik P. Patel
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Paraventricular Nucleus ◽  
Carotid Body ◽  
Coronary Artery Ligation ◽  
Nerve Activity ◽  
Artery Ligation ◽  
Peripheral Chemoreceptor ◽  
Arterial Blood ◽  
Peripheral Chemoreflex

Our previous study demonstrated a contribution of the paraventricular nucleus (PVN) of the hypothalamus in the processing of the carotid body (CB) chemoreflex. Nitric oxide (NO) (within the PVN), known to modulate autonomic function, is altered in rats with heart failure (HF). Therefore, the goal of the present study was to examine the influence of endogenous and exogenous NO within the PVN on the sympathoexcitatory component of the peripheral chemoreflex in normal and HF states. We measured mean arterial blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) in sham-operated and HF rats (6–8 wk after coronary artery ligation) after incremental doses of potassium cyanide (25–100 μg/kg iv). There was potentiation of the reflex responses in HF compared with sham-operated rats. Bilateral microinjection of an inhibitor of NO synthase, NG-monomethyl-l-arginine (50 pmol), into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation in sham-operated rats but had no effect in HF rats. Conversely, bilateral microinjection of a NO donor, sodium nitroprusside (50 nmol), into the PVN attenuated the RSNA response of the peripheral chemoreflex in sham-operated rats but to a smaller extent in HF rats. These data indicate that 1) NO within the PVN plays an important role in the processing of the CB chemoreflex and 2) there is an impairment of the NO function within the PVN of HF rats, which contributes to an augmented peripheral chemoreflex and subsequent elevation of sympathetic activity in HF.

NO is involved in MCh-induced accentuated antagonism via type II PDE in the canine blood-perfused SA node

2000 ◽  
Vol 279 (5) ◽  
pp. H2509-H2518 ◽  
Author(s):  
Shingo Sasaki ◽  
Kazuyuki Daitoku ◽  
Atsushi Iwasa ◽  
Shigeru Motomura
Keyword(s):  
Sinoatrial Node ◽  
Pacemaker Activity ◽  
Type Ii ◽  
Arterial Infusion ◽  
Arterial Blood ◽  
Endogenous Nitric Oxide ◽  
Camp Hydrolysis ◽  
The Right ◽  
Dose Dependent

The possible role of type II (cGMP-stimulated cAMP hydrolysis) phosphodiesterase (PDE) in the accentuated antagonism of muscarinic effects on heart rate during β-stimulation via endogenous nitric oxide (NO) was evaluated. The canine isolated sinoatrial node preparation was cross circulated with arterial blood of a support dog. The sinoatrial rate of the preparation was 96 ± 5 beats/min ( n = 16) at control. Methacholine (MCh; 0.01–1 μg) injected into the right coronary artery in a bolus fashion caused dose-dependent decreases in sinoatrial rate. Under an intra-arterial infusion of isoproterenol (1 μM), resulting in ∼50% increase in sinoatrial rate, MCh-induced decreases were markedly augmented from −18 ± 3% to −44 ± 4% at 0.3 mg of MCh. When N G-nitro-l-arginine methyl ester (100 μM) or N G-monomethyl-l-arginine (100 μM) were continuously infused, the augmented MCh-induced decreases in sinoatrial rate were significantly suppressed (−29 ± 3% or −25 ± 3%, respectively, P < 0.01). Pretreatment with either 3-isobutyl-1-methylxanthine (IBMX; 20 μM), a non-selective PDE inhibitor, or amrinone (20 μM), a selective type III (cGMP inhibited cAMP hydrolysis) PDE inhibitor, doubled the isoproterenol-induced increase in the sinoatrial rate. However, the augmented MCh-induced decreases in sinoatrial rate were significantly depressed by IBMX (from −23 ± 5% to −14 ± 1%, P < 0.01) but not by amrinone (to −20 ± 3%). These results suggest that MCh-induced accentuated antagonism in the sinoatrial node pacemaker activity can be modulated by endogenous NO via an activation of the type II cyclic GMP-stimulated cAMP PDE.

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