Leptin reduces plasma ANP level via nitric oxide-dependent mechanism

2010 ◽  
Vol 298 (4) ◽  
pp. R1007-R1016 ◽  
Author(s):  
Kuichang Yuan ◽  
Jiahua Yu ◽  
Amin Shah ◽  
Shan Gao ◽  
Sun Young Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Receptor Density ◽  
Sprague Dawley ◽  
Control Groups ◽  
Control Value ◽  
Sprague Dawley Rats ◽  
And Control ◽  
Dependent Mechanism

Leptin is a circulating adipocyte-derived hormone that influences blood pressure (BP) and metabolism. This study was designed to define the possible role of leptin in regulation of the atrial natriuretic peptide (ANP) system using acute and chronic experiments. Intravenous infusion of rat leptin (250 μg/kg injection plus 2 μg·kg−1·min−1 for 20 min) into Sprague-Dawley rats increased BP by 25 mmHg and decreased plasma level of ANP from 80.3 ± 3.45 to 51.8 ± 3.3 pg/ml. Reserpinization attenuated the rise in BP, but not the reduction of plasma ANP during leptin infusion. Nω-nitro-l-arginine methyl ester prevented the effects of leptin on the reduction of ANP level. In hyperleptinemic rats that received adenovirus containing rat leptin cDNA (AdCMV-leptin), BP increased during first 2 days and then recovered to control value. Plasma concentration of ANP and expression of ANP mRNA, but not of atrial ANP, in hyperleptinemic rats were lower than in the control groups on the first and second week after administration of AdCMV-leptin. These effects were not observed by the pretreatment with Nω-nitro-l-arginine methyl ester. No differences in renal function and ANP receptor density in the kidney were found between hyperleptinemic and control rats. Basal ANP secretion and isoproterenol-induced suppression of ANP secretion from isolated, perfused atria of hyperleptinemic rats were not different from those of other control groups. These data suggest that leptin inhibits ANP secretion indirectly through nitric oxide without changing basal or isoproterenol-induced ANP secretion.

scholarly journals Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

2014 ◽  
Vol 40 (4) ◽  
pp. 421-424 ◽  
Author(s):  
Igor Bastos Polonio ◽  
Milena Marques Pagliareli Acencio ◽  
Rogério Pazetti ◽  
Francine Maria de Almeida ◽  
Bárbara Soares da Silva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Experimental Model ◽  
Ventricular Hypertrophy ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Sprague Dawley ◽  
Control Groups ◽  
Right Heart ◽  
Sprague Dawley Rats ◽  
And Control

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

scholarly journals Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ketab E. Al-Otaibi ◽  
Abdulrahman M. Al Elaiwi ◽  
Mohammad Tariq ◽  
Abdulrahman K. Al-Asmari
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Femoral Vein ◽  
Lipid Hydroperoxides ◽  
Sprague Dawley ◽  
Glycerol Injection ◽  
Sprague Dawley Rats ◽  
Structural Abnormalities ◽  
Nephroprotective Effect

Contrast media- (CM-) induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN). Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg) with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg) was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg) through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels) and myeloperoxidase (MPO) and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

Role of distal delivery of filtrate in impaired renal dilution of the hypothyroid rat

1976 ◽  
Vol 230 (3) ◽  
pp. 699-705 ◽  
Author(s):  
UF Michael ◽  
J Kelley ◽  
H Alpert ◽  
CA Vaamonde
Keyword(s):  
Free Water ◽  
Urine Flow ◽  
Distal Nephron ◽  
Sprague Dawley ◽  
Diluting Segment ◽  
Free Water Clearance ◽  
Sprague Dawley Rats ◽  
And Control ◽  
Distal Delivery

Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron.

Nitric Oxide in the Gracile Nucleus Mediates Depressor Response to Acupuncture (ST36)

2003 ◽  
Vol 90 (2) ◽  
pp. 780-785 ◽  
Author(s):  
Shuang Chen ◽  
Sheng-Xing Ma
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Gracile Nucleus ◽  
Sprague Dawley Rats ◽  
Antisense Oligos ◽  
Stimulation Of

The purpose of these studies was to determine the role of gracile nucleus and the effects of l-arginine-derived nitric oxide (NO) synthesis in the nucleus on the cardiovascular responses to electroacupuncture (EA) stimulation of “Zusanli” (ST36). Arterial blood pressure and heart rate were monitored during EA stimulation of ST36 following microinjections of agents into gracile nucleus. EA ST36 produced depressor and bradycardiac responses in anesthetized Sprague-Dawley rats. The cardiovascular responses to EA ST36 were blocked by bilateral microinjection of lidocaine into gracile nucleus. Microinjection of l-arginine into gracile nucleus facilitated the hypotensive and bradycardiac responses to EA ST36. The cardiovascular responses to EA ST36 were attenuated by bilateral microinjection of neuronal NO synthase (nNOS) antisense oligos into gracile nucleus. Microinjection of nNOS sense oligos into gracile nucleus did not alter the cardiovascular response to EA ST36. The results demonstrate that a blockade of neuronal conduction in the gracile nucleus inhibits the cardiovascular responses to EA ST36. The hypotensive and bradycardiac responses to EA ST36 are modified by influences of l-arginine-derived NO synthesis in the gracile nucleus. We conclude that NO plays an important role in mediating the cardiovascular responses to EA ST36 through gracile nucleus.

scholarly journals Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents

2011 ◽  
Vol 301 (5) ◽  
pp. R1529-R1539 ◽  
Author(s):  
Annie M. Whitaker ◽  
Jesse K. Sulzer ◽  
Patricia E. Molina
Keyword(s):  
Nitric Oxide ◽  
Alcohol Intoxication ◽  
Sprague Dawley ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasopressin Release ◽  
No Inhibition ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300–325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg−1·h−1) or dextrose prior to a 60-min fixed-pressure hemorrhage (∼40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg−1·min−1). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition.

Inhibition of nitric oxide synthesis increases venular permeability and alters endothelial actin cytoskeleton

1998 ◽  
Vol 274 (5) ◽  
pp. H1776-H1784 ◽  
Author(s):  
Ann L. Baldwin ◽  
Gavin Thurston ◽  
Hamda Al Naemi
Keyword(s):  
Nitric Oxide ◽  
Mast Cells ◽  
Methyl Ester ◽  
Actin Cytoskeleton ◽  
Cell Junctions ◽  
Sprague Dawley ◽  
Filamentous Actin ◽  
Cellular Mechanisms ◽  
Rat Mesentery ◽  
Sprague Dawley Rats

Inhibition of nitric oxide (NO) synthesis using N G-nitro-l-arginine methyl ester (l-NAME) or N G-monomethyl-l-arginine (l-NMMA) increases venular permeability in the rat mesentery (I. Kurose, R. Wolf, M. B. Grisham, T. Y. Aw, R. D. Specian, and D. N. Granger. Circ. Res. 76: 30–39, 1995), but the cellular mechanisms of this response are not known. This study was performed to determine whether such venular leaks are associated with changes in the endothelial actin cytoskeleton. In anesthetized Sprague-Dawley rats, the microvasculature of a mesenteric window was perfused with buffered saline, with or without 10−5M l-NAME,l-NMMA, or the inactive enantiomer N G-nitro-d-arginine methyl ester for 3 or 30 min. FITC-albumin was added to the perfusate for the last 3 min. The vasculature was perfusion fixed, stained for filamentous actin and for mast cells, and viewed microscopically. In control preparations, venules showed few FITC-albumin leaks and the endothelial actin cytoskeleton consisted of a peripheral rim along the cell-cell junctions. Preparations treated withl-NAME orl-NMMA showed significantly more leakage, the actin rims in leaky venules were discontinuous, and short, randomly oriented fibers appeared within the cells. In nonleaky venules, the peripheral actin rims sometimes contained small, equally spaced discontinuities not seen in control preparations. Although a mast cell stabilizer was used, 27–70% of the mast cells were degranulated in the presence ofl-NMMA. Thus inhibition of NO synthesis alters the endothelial cytoskeleton and increases albumin leakage from mesenteric venules, either directly or indirectly via the involvement of mast cells.

Acute superoxide scavenging reduces sympathetic vasoconstrictor responsiveness in short-term exercise-trained rats

2013 ◽  
Vol 114 (11) ◽  
pp. 1511-1518 ◽  
Author(s):  
Nicholas G. Jendzjowsky ◽  
Darren S. DeLorey
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Dependent Manner ◽  
Sympathetic Stimulation ◽  
Sprague Dawley ◽  
Vascular Conductance ◽  
Time Control ◽  
Sprague Dawley Rats ◽  
Vasoconstrictor Response ◽  
40 Hz

We hypothesized that acute superoxide (O2−) scavenging would attenuate sympathetic vasoconstrictor responsiveness by augmenting nitric oxide (NO)-mediated inhibition of sympathetic vasoconstriction in exercise-trained rats. Sprague-Dawley rats were randomly assigned to sedentary time control (S; n = 7) or mild- (M: 20 m/min, 5° grade; n = 7) or heavy-intensity (H: 40 m/min, 5° grade; n = 7) exercise training (ET) groups and trained 5 days/wk for 4 wk with matched training volume. Following ET, rats were anesthetized and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance. In resting skeletal muscle, the percentage change of femoral vascular conductance in response to continuous (2 Hz) and patterned (20 and 40 Hz) sympathetic stimulation was determined during control conditions, O2− scavenging (TIRON, 1 g·kg−1·h−1 iv) and combined O2− scavenging + nitric oxide synthase blockade ( Nω-nitro-l-arginine methyl ester, 5 mg/kg iv). ET augmented the vasoconstrictor response to sympathetic stimulation in a training intensity-dependent manner ( P < 0.05) (S: 2 Hz: −26 ± 7.1%; 20 Hz: −26.9 ± 7.3%; 40 Hz: −27.7 ± 7.0%; M: 2 Hz: −37.4 ± 8.3%; 20 Hz: −35.9 ± 7.4%; 40 Hz: −38.2 ± 9.4%; H: 2 Hz: −46.9 ± 7.8%; 20 Hz: −48.5 ± 7.2%; 40 Hz: −51.2 ± 7.3%). O2− scavenging did not alter ( P > 0.05) the vasoconstrictor response in S rats (S: 2 Hz: −23.9 ± 7.6%; 20 Hz: −26.1 ± 9.1%; 40 Hz: −27.5 ± 7.2%), whereas the response in ET rats was diminished (M: 2 Hz: −26.3 ± 5.1%; 20 Hz: −28.7 ± 5.3%; 40 Hz: −28.5 ± 5.6%; H: 2 Hz: −35.5 ± 10.3%; 20 Hz: −38.6 ± 6.8%; 40 Hz: −43.9 ± 5.9%, P < 0.05). TIRON + Nω-nitro-l-arginine methyl ester increased vasoconstrictor responsiveness ( P < 0.05) in ET rats (M: 2 Hz: −47.7 ± 9.8%; 20 Hz: −41.2 ± 7.2%; 40 Hz: −50.5 ± 7.9%; H: 2 Hz: −55.8 ± 7.6%; 20 Hz: −55.7 ± 7.8%; 40 Hz: −58.7 ± 6.2%), whereas, in S rats, the response was unchanged (2 Hz: −29.4 ± 8.7%; 20 Hz: −30.0 ± 7.4%; 40 Hz: −35.2 ± 10.3%; P > 0.05). These data indicate that the augmented sympathetic vasoconstrictor responsiveness in ET rats was related to increased oxidative stress and altered nitric oxide-mediated inhibition of vasoconstriction.

Roles of Free Radicals, Nitric Oxide, and Scavenging Enzymes in Nasal Polyp Development

2005 ◽  
Vol 114 (2) ◽  
pp. 122-126 ◽  
Author(s):  
Turgut Karlidaǧ ◽  
Erol Keles ◽  
Nevin İlhan ◽  
Sinasi Yakclin ◽  
İrfan Kaygusuz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nasal Polyp ◽  
Inferior Turbinate ◽  
Control Group ◽  
Free Oxygen Radicals ◽  
Control Groups ◽  
Free Radical Damage ◽  
Scavenging Enzymes ◽  
And Control

The aim of this study was to investigate the role of nitric oxide (NO), free oxygen radicals, and scavenging enzymes in the development of nasal polyp (NP) disease. This study included 41 patients who underwent endoscopic surgery because of NPs. Control specimens were taken from the inferior turbinate of 32 patients who underwent septoplasty. The levels of malondialdehyde (MDA), NO, and superoxide dismutase (SOD) were measured in intraoperative specimens of polyp tissue and turbinate mucosa. The levels of tissue NO were 191.06 ± 26.62 μmol/mg of protein in patients with NPs and 145.30 ± 19.19 μmol/mg of protein (p < .001) in the control group. The levels of MDA in the study and control groups were 12.47 ± 2.12 nmol/mg and 8.83 ± 1.08 nmol/mg (p < .01), respectively. The levels of SOD in the study and control groups were 50.77 ± 14.74 U/mg and 77.93 ± 15.31 U/mg (p < .001), respectively. It was determined that the levels of MDA in plasma and erythrocytes were higher in the patients with NPs than in the control group (p < .05). The levels of NO in plasma and erythrocytes in both groups were similar. The levels of SOD in plasma and erythrocytes were lower in patients with NPs than in the control group (p > .05). Increases in the levels of tissue MDA and NO and decreases in scavenging enzymes in patients with NPs as compared to control groups may indicate the presence of free radical damage in patients with nasal NPs. New studies are needed to clarify the efficacy of using antioxidants in the treatment of NPs.

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.

Superoxide mediates acute renal vasoconstriction produced by angiotensin II and catecholamines by a mechanism independent of nitric oxide

2007 ◽  
Vol 292 (1) ◽  
pp. H83-H92 ◽  
Author(s):  
Armin Just ◽  
Andrea J. M. Olson ◽  
Christina L. Whitten ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Vascular Remodeling ◽  
Oxygen Species ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Adrenergic Agonist ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats

NAD(P)H oxidases (NOX) and reactive oxygen species (ROS) are involved in vasoconstriction and vascular remodeling during hypertension produced by chronic angiotensin II (ANG II) infusion. These effects are thought to be mediated largely through superoxide anion (O2−) scavenging of nitric oxide (NO). Little is known about the role of ROS in acute vasoconstrictor responses to agonists. We investigated renal blood flow (RBF) reactivity to ANG II (4 ng), norepinephrine (NE, 20 ng), and α1-adrenergic agonist phenylephrine (PE, 200 ng) injected into the renal artery (ira) of anesthetized Sprague-Dawley rats. The NOX inhibitor apocynin (1–4 mg·kg−1·min−1 ira, 2 min) or the superoxide dismutase mimetic Tempol (1.5–5 mg·kg−1·min−1 ira, 2 min) rapidly increased resting RBF by 8 ± 1% ( P < 0.001) or 3 ± 1% ( P < 0.05), respectively. During NO synthase (NOS) inhibition ( Nω-nitro-l-arginine methyl ester, 25 mg/kg iv), the vasodilation tended to increase (apocynin 13 ± 4%, Tempol 10 ± 1%). During control conditions, both ANG II and NE reduced RBF by 24 ± 4%. Apocynin dose dependently reduced the constriction by up to 44% ( P < 0.05). Similarly, Tempol blocked the acute actions of ANG II and NE by up to 48–49% ( P < 0.05). In other animals, apocynin (4 mg·kg−1·min−1 ira) attenuated vasoconstriction to ANG II, NE, and PE by 46–62% ( P < 0.01). During NOS inhibition, apocynin reduced the reactivity to ANG II and NE by 60–72% ( P < 0.01), and Tempol reduced it by 58–66% ( P < 0.001). We conclude that NOX-derived ROS substantially contribute to basal RBF as well as to signaling of acute renal vasoconstrictor responses to ANG II, NE, and PE in normal rats. These effects are due to O2− rather than H2O2, occur rapidly, and are independent of scavenging of NO.

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