scholarly journals Preserved β-adrenergic mediated vasodilation in skeletal muscle of young obese adults despite shifts in cyclooxygenase and nitric oxide synthase

2021 ◽  
Author(s):  
Jaqueline K. Limberg ◽  
Rebecca E. Johansson ◽  
Katrina J Carter ◽  
Garrett Peltonen ◽  
John W Harrell ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Normal Weight ◽  
Control Mechanisms ◽  
Central Adiposity ◽  
Obese Adults ◽  
Arterial Blood ◽  
Forearm Vascular Conductance ◽  
Oxide Synthase

Central adiposity is associated with greater sympathetic support of blood pressure. β-adrenergic receptors (β-AR) buffer sympathetically-mediated vasoconstriction and β-AR mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized β-AR vasodilation would be lower in obese compared to normal weight adults. Because β-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to β-AR vasodilation in this cohort. Methods: Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance was calculated (FVC=FBF/MAP). The rise in FVC from baseline (ΔFVC) was quantified during graded brachial artery infusion of Isoproterenol (ISO, 1-12 ng/100g/min) in normal weight (n=36) and obese (n=22) adults (18-40 years old). In a subset of participants, ISO-mediated vasodilation was examined prior to and during inhibition of NOS (L-NMMA), COX (Ketorolac), and NOS + COX (L-NMMA + Ketorolac). Results: ISO-mediated increases in FVC did not differ between groups (p=0.57). L-NMMA attenuated ISO-mediated ΔFVC in normal weight (p=0.03) but not obese (p=0.27) adults. In normal weight adults, Ketorolac increased ISO-mediated ΔFVC (p<0.01) and this response was lost with concurrent L-NMMA (p=0.67). In contrast, neither Ketorolac (p=0.81) nor Ketorolac + L-NMMA (p=0.40) altered ISO-mediated ΔFVC in obese adults. Conclusion: Despite shifts in COX and NOS, β-AR vasodilation is preserved in young obese adults. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger obese humans.

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 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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