scholarly journals Effect of Nitric Oxide Blockade by NG-Nitro-l-Arginine on Cerebral Blood Flow Response to Changes in Carbon Dioxide Tension

1992 ◽  
Vol 12 (6) ◽  
pp. 947-953 ◽  
Author(s):  
Qiong Wang ◽  
Olaf B. Paulson ◽  
Niels A. Lassen
Keyword(s):  
Nitric Oxide ◽  
Carbon Dioxide ◽  
Blood Pressure ◽  
Control Level ◽  
Inhibitory Effect ◽  
Carbon Dioxide Tension ◽  
Extracellular Acidosis ◽  
Flow Response ◽  
Arterial Blood ◽  
Oxide Synthase

The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-l-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 ± 10 to 78 ± 6, 64 ± 5, and 52 ± 5 ml 100g−1 min−1, respectively. This effect lasted for at least 2 h. Raising Paco2 from a control level of 40 to 68 mm Hg increased CBF to 230 ± 27 ml 100g−1 min−1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 ± 0.6%/mm Hg Paco2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. l-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. d-Arginine had no such effect. Decreasing Paco2 to 20 mm Hg reduced control CBF to 46 ± 3 ml 100g−1 min−1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg). The results suggest that NO or a closely related compound is involved in the regulation of CBF in normocapnia and even more so in hypercapnia.

scholarly journals Association of endothelial nitric oxide synthase (eNOS) gene polymorphisms and physical fitness levels with plasma nitrite concentrations and arterial blood pressure values in older adults

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0206254
Author(s):  
Roberta Fernanda da Silva ◽  
Átila Alexandre Trapé ◽  
Thaís Amanda Reia ◽  
Riccardo Lacchini ◽  
Gustavo Henrique Oliveira-Paula ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Older Adults ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Polymorphisms ◽  
Enos Gene ◽  
Arterial Blood ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Blunted respiratory responses to hypoxia in mutant mice deficient in nitric oxide synthase-3

2000 ◽  
Vol 88 (4) ◽  
pp. 1496-1508 ◽  
Author(s):  
David D. Kline ◽  
Tianen Yang ◽  
Daniel R. D. Premkumar ◽  
Agnes J. Thomas ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Blood Gases ◽  
Mutant Mice ◽  
No Production ◽  
Experimental Conditions ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
Respiratory Responses

In the present study, the role of nitric oxide (NO) generated by endothelial nitric oxide synthase (NOS-3) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-3. Experiments were performed on awake and anesthetized mutant and wild-type (WT) control mice. Respiratory responses to 100, 21, and 12% O2and 3 and 5% CO2-balance O2were analyzed. In awake animals, respiration was monitored by body plethysmography along with O2consumption (V˙o2) and CO2production (V˙co2). In anesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Under both experimental conditions, WT mice responded with greater increases in respiration during 12% O2than mutant mice. Respiratory responses to hyperoxic hypercapnia were comparable between both groups of mice. Arterial blood gases, changes in blood pressure,V˙o2, andV˙co2during hypoxia were comparable between both groups of mice. Respiratory responses to cyanide and brief hyperoxia were attenuated in mutant compared with WT mice, indicating reduced peripheral chemoreceptor sensitivity. cGMP levels in the brain stem during 12% O2, taken as an index of NO production, were greater in mutant compared with WT mice. These observations demonstrate that NOS-3 mutant mice exhibit selective blunting of the respiratory responses to hypoxia but not to hypercapnia, which in part is due to reduced peripheral chemosensitivity. These results support the idea that NO generated by NOS-3 is an important physiological modulator of respiration during hypoxia.

Effect of Antioxidant Therapy on Nitric Oxide Synthase (NOS) Expression in Hypertensive Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 705-705
Author(s):  
Nosratola D Vaziri ◽  
Zhenmin Ni ◽  
Debra L Trnavsky-Hobbs ◽  
Fariba Oveisi
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Inos Expression ◽  
Antioxidant Therapy ◽  
No Production ◽  
Hypertensive Rats ◽  
Negative Feedback Regulation ◽  
Arterial Blood ◽  
Oxide Synthase

P66 Earlier studies have demonstrated evidence for increased reactive oxygen species (ROS) and enhanced nitric oxide synthase (NOS) expression and NO production in spontaneously hypertensive rats (SHR). Given the negative feedback regulation of NOS by NO, we hypothesized that enhanced NO inactivation by ROS may contribute to compensatory upregulation of NOS in SHR. The present study was designed to test this hypothesis. Eight-week old male SHR were treated for three weeks with either a placebo or the potent antioxidant, lazaroid (des-methyltirilazad, 10 mg/kg/day by gastric gavage). A group of age-matched male Wistar Kyoto (WKY) rats served as controls. Tail arterial blood pressure and urinary excretion of NO metabolites (i.e. nitrate and nitrite, NO x ) were measured. In addition, immunodetectable NOS isotype proteins in the vascular, renal, cardiac and cerebral tissues were measured by Western blot. Compared to the WKY group, the placebo-treated SHR group showed a marked elevation of blood pressure (129±6 vs 198±8 mmHg, P<0.01), a significant increase in urinary NOx excretion (714±82 vs 1344±187 μmol/g creatinine, P<0.01) and a significant upregulation of eNOS (given as relative optical density) in the aorta (27±3 vs 165±15*), kidney (99±3 vs 180±8*) and heart (17±4 vs 126±2*). Likewise, inducible NOS (iNOS) expression was increased in the aorta (27±3 vs 163±15*), kidney (7±3 vs 322±57*)and heart (30±1 vs 80±2*) of the untreated SHR when compared to the WKY controls. In addition, nNOS expression was elevated in the brain (10±1 vs 18±1*) and kidney (12±1 vs 20±2*) of the untreated SHR group. Lazaroid therapy ameliorated HTN (144±4 mmHg, P<0.01, vs untreated SHR group) and mitigated upregulation of eNOS in the aorta (85±13*), kidney (129±8*) and heart (59±10*). Similarly, antioxidant therapy lowered iNOS expression in the aorta (85±13*), kidney (99±15*) and heart (41±3*) of the treated SHR. However, it had no significant effect on renal and brain nNOS expressions (18±2 and 16±2, respectively). These findings support the role of oxidative stress in the genesis and/or maintenance of HTN and compensatory up-regulations of eNOS and iNOS expressions in SHR. *P<0.05

scholarly journals Effects of Inhibition of Nitric Oxide Synthase on Muscular Arteries During Exercise: Nitric Oxide Does Not Contribute to Vasodilation During Exercise or in Recovery

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Kevin O'Gallagher ◽  
Husain Shabeeh ◽  
Shahzad Munir ◽  
Ali Roomi ◽  
Benyu Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
Femoral Artery ◽  
Peripheral Resistance ◽  
Muscular Artery ◽  
Arterial Blood ◽  
Exercise Hemodynamics ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Background Basal release of nitric oxide ( NO ) from the vascular endothelium regulates the tone of muscular arteries and resistance vasculature. Effects of NO on muscular arteries could be particularly important during exercise when shear stress may stimulate increased NO synthesis. Methods and Results We investigated acute effects of NO synthase inhibition on exercise hemodynamics using N G ‐monomethyl‐ l ‐arginine ( l ‐ NMMA ), a nonselective NO synthase ‐inhibitor. Healthy volunteers (n=10, 5 female, 19–33 years) participated in a 2‐phase randomized crossover study, receiving l ‐ NMMA (6 mg/kg, iv over 5 minutes) or placebo before bicycle exercise (25–150 W for 12 minutes). Blood pressure, cardiac output (measured by dilution of soluble and inert tracers) and femoral artery diameter were measured before, during, and after exercise. At rest, l ‐ NMMA reduced heart rate (by 16.2±4.3 bpm relative to placebo, P <0.01), increased peripheral vascular resistance (by 7.0±1.4 mmHg per L/min, P <0.001), mean arterial blood pressure (by 8.9±3.5 mmHg, P <0.05), and blunted an increase in femoral artery diameter that occurred immediately before exercise (change in diameter: 0.14±0.04 versus 0.32±0.06 mm after l ‐ NMMA and placebo, P <0.01). During/after exercise l ‐ NMMA had no significant effect on peripheral resistance, cardiac output, or on femoral artery diameter. Conclusions These results suggest that NO plays little role in modulating muscular artery function during exercise but that it may mediate changes in muscular artery tone immediately before exercise.

Platelet-activating factor and solute transport processes in the kidney

2003 ◽  
Vol 284 (2) ◽  
pp. F274-F281 ◽  
Author(s):  
Rajash K. Handa ◽  
Jack W. Strandhoy ◽  
Carlos E. Giammattei ◽  
Shelly E. Handa
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Proximal Tubule ◽  
Sodium Transport ◽  
Platelet Activating Factor ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
Cytochrome P 450

We examined the hemodynamic and tubular transport mechanisms by which platelet-activating factor (PAF) regulates salt and water excretion. In anesthetized, renally denervated male Wistar rats, with raised systemic blood pressure and renal arterial blood pressure maintained at normal levels, intrarenal PAF infusion at 2.5 ng · min−1 · kg−1resulted in a small fall in systemic blood pressure (no change in renal arterial blood pressure) and an increase in renal blood flow and urinary water, sodium, and potassium excretion rates. The PAF-induced changes in cardiovascular and renal hemodynamic function were abolished and renal excretory function greatly attenuated by treating rats with a nitric oxide synthase inhibitor. To determine whether a tubular site of action was involved in the natriuretic effect of PAF, cortical proximal tubules were enzymatically dissociated from male Wistar rat kidneys, and oxygen consumption rates (Qo 2) were used as an integrated index of transcellular sodium transport. PAF at 1 nM maximally inhibited Qo 2 in both untreated and nystatin-stimulated (sodium entry into renal cell is not rate limiting) proximal tubules by ∼20%. Blockade of PAF receptors or Na+-K+-ATPase pump activity with BN-52021 or ouabain, respectively, abolished the effect of PAF on nystatin-stimulated proximal tubule Qo 2. Inhibition of nitric oxide synthase or guanylate cyclase systems did not alter PAF-mediated inhibition of nystatin-stimulated proximal tubule Qo 2, whereas phospholipase A2 or cytochrome- P-450 monooxygenase inhibition resulted in a 40–60% reduction. These findings suggest that stimulation of PAF receptors on the proximal tubule decreases transcellular sodium transport by activating phospholipase A2 and the cytochrome- P-450 monooxygenase pathways that lead to the inhibition of an ouabain-sensitive component of the basolateral Na+-K+-ATPase pump. Thus PAF can activate both an arachidonate pathway-mediated suppression of proximal tubule sodium transport and a nitric oxide pathway-mediated dilatory action on renal hemodynamics that likely contributes to the natriuresis and diuresis observed in vivo.

eNOS involved in colitis-induced mucosal blood flow increase

2007 ◽  
Vol 293 (6) ◽  
pp. G1281-G1287 ◽  
Author(s):  
Joel Petersson ◽  
Olof Schreiber ◽  
Andreas Steege ◽  
Andreas Patzak ◽  
Anna Hellsten ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Control Level ◽  
Mucosal Blood Flow ◽  
Control Group ◽  
Trinitrobenzene Sulfonic Acid ◽  
Doppler Flowmetry ◽  
Arterial Blood

The role of NO in inflammatory bowel disease is controversial. Studies indicate that endothelial nitric oxide synthase (eNOS) might be involved in protecting the mucosa against colonic inflammation. The aim of this study was to investigate the involvement of nitric oxide (NO) in regulating colonic mucosal blood flow in two different colitis models in rats. In anesthetized control and colitic rats, the distal colon was exteriorized and the mucosa visualized. Blood flow (laser-Doppler flowmetry) and arterial blood pressure were continuously monitored throughout the experiments, and vascular resistance was calculated. Trinitrobenzene sulfonic acid (TNBS) or dextran sulfate sodium (DSS) was used to induce colitis. All groups were given the NOS inhibitor Nω-nitro-l-arginine (l-NNA) or the inducible NOS (iNOS) inhibitor l- N6-(1-iminoethyl)-lysine (l-NIL). iNOS, eNOS, and neuronal NOS (nNOS) mRNA in colonic samples were investigated with real-time RT-PCR. Before NOS inhibition, colonic mucosal blood flow, expressed as perfusion units, was higher in both colitis models compared with the controls. The blood flow was reduced in the TNBS- and DSS-treated rats during l-NNA administration but was not altered in the control group. Vascular resistance increased more in the TNBS- and DSS-treated rats than in the control rats, indicating a higher level of vasodilating NO in the colitis models. l-NIL did not alter blood pressure or blood flow in any of the groups. iNOS and eNOS mRNA increased in both colitis models, whereas nNOS remained at the control level. TNBS- and DSS-induced colitis results in increased colonic mucosal blood flow, most probably due to increased eNOS activity.

scholarly journals Effect of an Inhibitor of Neuronal Nitric Oxide Synthase 7-Nitroindazole on Cerebral Hemodynamic Response and Brain Excitability in Urethane-Anesthetized Rats

2013 ◽  
pp. S57-S66 ◽  
Author(s):  
C. BROŽÍČKOVÁ ◽  
J. OTÁHAL
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Neurovascular Coupling ◽  
Neuronal Nitric Oxide Synthase ◽  
Hemodynamic Response ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Oxide Synthase

The role of neuronal nitric oxide synthase (nNOS) in the pathophysiology of epilepsy and seizures remains disputable. One of the reasons why results from the acute in vivo studies display controversies might be the effect on the regulation of cerebral blood flow (CBF) during pharmacologically induced alterations of NO system. We examined neurovascular coupling in the rat sensorimotor cortex in response to transcallosal stimulation under nNOS inhibition by 7-nitroindazole (7-NI). Adult Wistar rats were anesthetized with urethane and epidural silver EEG electrodes were implanted over sensorimotor cortices. Regional CBF was measured by Laser Doppler Flowmetry (LDF). We catheterized a common carotid artery to measure arterial blood pressure (BP). 7-NI did not significantly affect blood pressure and heart rate. Electrophysiological recordings of evoked potentials (EPs) revealed no effect on their amplitude, rhythmic potentiation or depression of EPs. Transcallosal stimulation of the contralateral cortex induced a frequency dependent rise in CBF. Although 7-NI did not significantly affect basal CBF and cortical excitability, hemodynamic responses to the transcallosal stimulation were diminished implicating a role of nNOS in neurovascular coupling. Urethane anesthesia is suitable for future epileptological experiments. Our findings demonstrate that NO contributes to the hemodynamic response during brain activation.

Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock

1996 ◽  
Vol 81 (2) ◽  
pp. 707-715 ◽  
Author(s):  
A. Vromen ◽  
C. Szabo ◽  
G. J. Southan ◽  
A. L. Salzman
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Hemorrhagic Shock ◽  
Renal Perfusion ◽  
Beneficial Effects ◽  
Arterial Blood ◽  
Nos Inhibitor ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

We characterized the response to intravenous S-isopropyl isothiourea (IPTU), a novel potent nitric oxide synthase (NOS) inhibitor, in rodent and porcine models of hemorrhagic shock (HS). IPTU (at 300 micrograms/kg, administered as 3 subsequent bolus injections), in anesthetized rats hemorrhaged to a mean arterial blood pressure (MAP) of 35 mmHg, increased MAP and improved survival over 120 min. In anesthetized pigs hemorrhaged to a MAP of 45 mmHg, IPTU (0.3 mg/kg plus 1 mg.kg-1.h-1) increased MAP and systemic vascular resistance. IPTU did not alter the cardiac index, renal blood flow, arterial and portal oxygen content, or splanchnic oxygen consumption or extraction. In contrast, infusion of norepinephrine (100 micrograms.kg-1.h-1) did not alter MAP and increased mortality in the rat model, whereas it caused a transient increase in MAP and a tachycardia in the porcine model of HS without significantly affecting the other parameters studied. Inhibition of the endothelial NOS in early severe HS may have beneficial effects on blood pressure and survival without altering cardiac output and splanchnic and renal perfusion.

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