scholarly journals Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Walter J. May ◽  
Graham C. von Schill ◽  
Dylan K. McLaughlin ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Whole Body ◽  
Inspiratory Time ◽  
Male And Female ◽  
Knock Out ◽  
Ventilatory Responses ◽  
Knock Out Mice ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

AbstractThe roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

Ventilatory Responses During and Following Hypercapnic Gas Challenge are Impaired in Male but Not Female Endothelial NOS Knock-out Mice

2021 ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Walter J. May ◽  
Graham vonSchill ◽  
Dylan K. McLaughlin ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Inspiratory Time ◽  
Male And Female ◽  
Knock Out ◽  
Ventilatory Responses ◽  
Freely Moving ◽  
Knock Out Mice ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was equal in male and female WT mice. However, the post-HCC increases in frequency of breathing (and decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory and expiratory drives, and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

scholarly journals Short-term facilitation of breathing upon cessation of hypoxic challenge is impaired in male but not female endothelial NOS knock-out mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Walter J. May ◽  
Graham C. von Schill ◽  
Dylan K. McLaughlin ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Short Term ◽  
Male And Female ◽  
Knock Out ◽  
Functional Roles ◽  
Ventilatory Responses ◽  
Arterial Blood ◽  
Term Potentiation ◽  
Arterial Blood Oxygen ◽  
Knock Out Mice

AbstractDecreases in arterial blood oxygen stimulate increases in minute ventilation via activation of peripheral and central respiratory structures. This study evaluates the role of endothelial nitric oxide synthase (eNOS) in the expression of the ventilatory responses during and following a hypoxic gas challenge (HXC, 10% O2, 90% N2) in freely moving male and female wild-type (WT) C57BL6 and eNOS knock-out (eNOS–/–) mice. Exposure to HXC caused an array of responses (of similar magnitude and duration) in both male and female WT mice such as, rapid increases in frequency of breathing, tidal volume, minute ventilation and peak inspiratory and expiratory flows, that were subject to pronounced roll-off. The responses to HXC in male eNOS–/– mice were similar to male WT mice. In contrast, several of the ventilatory responses in female eNOS–/– mice (e.g., frequency of breathing, and expiratory drive) were greater compared to female WT mice. Upon return to room-air, male and female WT mice showed similar excitatory ventilatory responses (i.e., short-term potentiation phase). These responses were markedly reduced in male eNOS–/– mice, whereas female eNOS–/– mice displayed robust post-HXC responses that were similar to those in female WT mice. Our data demonstrates that eNOS plays important roles in (1) ventilatory responses to HXC in female compared to male C57BL6 mice; and (2) expression of post-HXC responses in male, but not female C57BL6 mice. These data support existing evidence that sex, and the functional roles of specific proteins (e.g., eNOS) have profound influences on ventilatory processes, including the responses to HXC.

Abstract 347: eNOS Deficiency Ameliorates Vascular Remodeling Induced by Periadventitial Injury in SOD1 Knock-Out Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Keiichiro Kataoka ◽  
Masaya Fukuda ◽  
Eiichiro Yamamoto ◽  
Taishi Nakamura ◽  
Hisao Ogawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Remodeling ◽  
List Type ◽  
Neointimal Formation ◽  
Knock Out ◽  
Copper Zinc ◽  
Knock Out Mice ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Deficient Mice

Background: Copper/zinc SOD (SOD1) is a major enzyme which deactivates superoxide radicals (O2−), and endothelial nitric oxide synthase (eNOS) synthesizes nitric oxide (NO) in endothelial cells. Reduction of each enzyme can increase oxidative stress, leading to cardiovascular dysfunction. Herein, we established SOD1 and eNOS double deficient mice, and examined their physiological and pathological cardiovascular phenotypes to clarify the function of eNOS in cardiovascular system in the case of SOD1 deficiency. Methods and Results: SOD1 deficient mice (SOD-KO) were crossbred with eNOS deficient mice (eNOS-KO), and SOD1 and eNOS double-deficient mice (Do-KO) were established. Do-KO had significantly higher blood pressure (BP) than SOD-KO (129.6 ± 4.7 vs. 102.1 ± 1.2 mmHg, p<0.0001). Do-KO had significantly higher heart weights than SOD-KO (3.12 ± 0.09 vs. 2.89 ± 0.03 mg/g, p<0.01). Relaxation of carotid arteries due to acetylcholine was mildly impaired in SOD-KO when compared with wild type mice (WT), while relaxation to acetylcholine was completely ablated in Do-KO. These data indicated that targeted ablation of eNOS in SOD-KO impaired their vascular relaxation, and caused hypertension. Next, we examined vascular remodeling induced by periadventitial cuff-injuries. Four weeks after cuff replacement, marked neointimal formation was induced in SOD-KO; however, eNOS deficiency in SOD-KO ameliorated the vascular remodeling of SOD-KO, and significantly decreased the ratio of intimal to medial areas (1.23 ± 0.23 vs. 2.23 ± 0.38, p<0.05). This data shows that eNOS enhances the vascular remodeling of SOD-KO caused by cuff injury. NO and O2− react to form the strong oxidant peroxynitrite, which is involved in vascular injury. The levels of 3-nitrotyrosine, a marker of peroxynitrite generation, were significantly elevated in the injured arteries of SOD-KO, while their elevation were attenuated in Do-KO. This indicates that NO derived from eNOS enhances the peroxynitrite formation in injured arteries of SOD-KO, so that vascular remodeling may be markedly enhanced. Conclusion: Our results demonstrate that peroxynitrite, generated from O2− and eNOS derived-NO, plays a key role in vascular remodeling induced by periadventitial injury.

scholarly journals ET-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice

Life Sciences ◽  
2013 ◽  
Vol 93 (25-26) ◽  
pp. e13
Author(s):  
Nicolas Vignon-Zellweger ◽  
Katharina Relle ◽  
Jan Rahnenfuhrer ◽  
Karima Schwab ◽  
Berthold Hocher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Male And Female ◽  
Knock Out ◽  
Female Mice ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Role of the carotid bodies in chemosensory ventilatory responses in the anesthetized mouse

2004 ◽  
Vol 97 (4) ◽  
pp. 1401-1407 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Mieczyslaw Pokorski ◽  
Ikuo Homma
Keyword(s):  
Tidal Volume ◽  
Carotid Body ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Whole Body ◽  
Sudden Increase ◽  
Ventilatory Responses ◽  
Carotid Bodies ◽  
Before And After ◽  
Carotid Body Denervation

We examined the effects of carotid body denervation on ventilatory responses to normoxia (21% O2 in N2 for 240 s), hypoxic hypoxia (10 and 15% O2 in N2 for 90 and 120 s, respectively), and hyperoxic hypercapnia (5% CO2 in O2 for 240 s) in the spontaneously breathing urethane-anesthetized mouse. Respiratory measurements were made with a whole body, single-chamber plethysmograph before and after cutting both carotid sinus nerves. Baseline measurements in air showed that carotid body denervation was accompanied by lower minute ventilation with a reduction in respiratory frequency. On the basis of measurements with an open-circuit system, no significant differences in O2 consumption or CO2 production before and after chemodenervation were found. During both levels of hypoxia, animals with intact sinus nerves had increased respiratory frequency, tidal volume, and minute ventilation; however, after chemodenervation, animals experienced a drop in respiratory frequency and ventilatory depression. Tidal volume responses during 15% hypoxia were similar before and after carotid body denervation; during 10% hypoxia in chemodenervated animals, there was a sudden increase in tidal volume with an increase in the rate of inspiration, suggesting that gasping occurred. During hyperoxic hypercapnia, ventilatory responses were lower with a smaller tidal volume after chemodenervation than before. We conclude that the carotid bodies are essential for maintaining ventilation during eupnea, hypoxia, and hypercapnia in the anesthetized mouse.

scholarly journals Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice

Life Sciences ◽  
2014 ◽  
Vol 118 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Nicolas Vignon-Zellweger ◽  
Katharina Relle ◽  
Jan Rahnenführer ◽  
Karima Schwab ◽  
Berthold Hocher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Male And Female ◽  
Knock Out ◽  
Female Mice ◽  
Endothelin 1 ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Increased cardiac microvascular permeability and activation of cardiac endothelial nitric oxide synthase in high tidal volume ventilation-induced lung injury

2010 ◽  
Vol 4 (1) ◽  
pp. 27-36
Author(s):  
Ming-Jui Hung ◽  
Ming-Yow Hung ◽  
Wen-Jin Cherng ◽  
Li-Fu Li
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lung Injury ◽  
Tidal Volume ◽  
Endothelial Nitric Oxide Synthase ◽  
Microvascular Permeability ◽  
Akt Phosphorylation ◽  
Enos Phosphorylation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract Background: Positive pressure ventilation with large tidal volumes has been shown to cause lung injury via the serine/threonine kinase-protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS)-pathways. However, the effects of high tidal volume (VT) ventilation on the heart are unclear. Objectives: Evaluate the effect of VT ventilation on the cardiac vascular permeability and intracellular Akt and eNOS signaling pathway. Methods: C57BL/6 and Akt knock-out (heterozygotes, +/−) mice were exposed to high VT (30 mL/kg) mechanical ventilation with room air for one and/or five hours. Results: High VT ventilation increased cardiac microvascular permeability and eNOS phosphorylation in a timedependent manner. Serum cardiac troponin I was increased after one hour of high VT ventilation. Cardiac Akt phosphorylation was accentuated after one hour and attenuated after five hours of high VT ventilation. Pharmacological inhibition of Akt with LY294002 and high VT ventilation of Akt+/− mice attenuated cardiac Akt phosphorylation, but not eNOS phosphorylation. Conclusion: High VT ventilation increased cardiac myocardial injury, microvascular permeability, and eNOS phosphorylation. Involvement of cardiac Akt in high VT ventilation was transient.

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