scholarly journals Nitric Oxide Depletion during Acute Hypoxia Causes Leukocyte Adherence to the Rat Mesenteric Venule

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 264A-264A
Author(s):  
Leone F Mattioli ◽  
John G Wood ◽  
Jennifer S Johnson ◽  
Norberto C Gonzalez
Keyword(s):  
Nitric Oxide ◽  
Acute Hypoxia ◽  
Leukocyte Adherence ◽  
Mesenteric Venule

Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence during acute hypoxia

2001 ◽  
Vol 91 (3) ◽  
pp. 1160-1167 ◽  
Author(s):  
Dawn R. S. Steiner ◽  
Norberto C. Gonzalez ◽  
John G. Wood
Keyword(s):  
Acute Hypoxia ◽  
Leukotriene B4 ◽  
Ros Generation ◽  
Leukocyte Adherence ◽  
Systemic Hypoxia ◽  
Microvascular Alterations ◽  
Reactive Oxidant ◽  
Underlying Mechanisms ◽  
Mesenteric Microcirculation

Acute systemic hypoxia produces rapid leukocyte adherence in the rat mesenteric microcirculation, although the underlying mechanisms are not fully known. Hypoxia is known to increase reactive oxygen species (ROS) generation, which could result in formation of the lipid inflammatory mediator leukotriene B4 (LTB4). The goal of this study was to examine the role of LTB4 in hypoxia-induced microvascular alterations. Using intravital microscopy, we determined the effect of the LTB4 antagonist, LTB4-dimethyl amide (LTB4-DMA), on ROS generation and leukocyte adherence in mesenteric venules during hypoxia. Exogenous LTB4 increased ROS generation to 144 ± 8% compared with control values and also promoted leukocyte adherence. These responses to LTB4 were blocked by pretreating the mesentery with LTB4-DMA. Leukopenia did not significantly attenuate the LTB4-induced increase in ROS generation (142 ± 12.1%). LTB4-DMA substantially, though not completely, reduced hypoxia-induced ROS generation from 66 ± 18% to 11 ± 4% above control values. Hypoxia-induced leukocyte adherence was significantly attenuated by LTB4-DMA. Our results support a role for LTB4in the mechanism of hypoxia-induced ROS generation and leukocyte adherence in the rat mesenteric microcirculation.

Search for an animal model to investigate selective pulmonary vasodilation

2016 ◽  
Vol 51 (4) ◽  
pp. 376-387
Author(s):  
Bodil Petersen ◽  
Thilo Busch ◽  
Katharina Noreikat ◽  
Lorenz Homeister ◽  
Ralf Regenthal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Animal Models ◽  
Vascular Tone ◽  
Acute Hypoxia ◽  
Haemodynamic Instability ◽  
Time Interval ◽  
Systemic Hypotension ◽  
Pulmonary Vasodilation ◽  
Selective Pulmonary Vasodilation

Pulmonary arterial hypertension is a life-threatening disease with a poor prognosis. Oral treatment with vasodilators is often limited by systemic hypotension. Inhalation of vasodilators offers the opportunity for selective pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled nitric oxide or alternative substances in animal models requires an increased pulmonary vascular tone. The aim of this study was to identify animal models that are suitable for investigating selective pulmonary vasodilation. To do so, a haemodynamic stable pulmonary hypertension was initiated, with a 30 min duration deemed to be a sufficient time interval before and after a possible intervention. In anaesthetized and mechanically-ventilated Sprague–Dawley rats pulmonary hypertension was induced either by acute hypoxia due to reduction of the inspired oxygen fraction from 0.21 to 0.1 ( n = 6), a fixed infusion rate of the thromboxane analogue U46619 (240 ng/min; n = 6) or a monocrotaline injection (MCT; 60 mg/kg applied 23 days before the investigation; n = 7). The animals were instrumented to measure right ventricular and systemic arterial pressures. Acute hypoxia caused a short, and only transient, increase of pulmonary artery pressure as well as profound systemic hypotension which suggested haemodynamic instability. U46619 infusion induced variable changes in the pulmonary and systemic vascular tone without sufficient stabilization within 30 min. MCT provoked sustained pulmonary hypertension with normal systemic pressure values and inhalation of nitric oxide caused selective pulmonary vasodilation. In conclusion, out of the three examined rat animal models only MCT-induced pulmonary hypertension is a solid and reliable model for investigating selective pulmonary vasodilation.

scholarly journals Acute hypoxia activates neuroendocrine, but not presympathetic, neurons in the paraventricular nucleus of the hypothalamus: differential role of nitric oxide

2017 ◽  
Vol 312 (6) ◽  
pp. R982-R995 ◽  
Author(s):  
K. Max Coldren ◽  
De-Pei Li ◽  
David D. Kline ◽  
Eileen M. Hasser ◽  
Cheryl M. Heesch
Keyword(s):  
Nitric Oxide ◽  
Paraventricular Nucleus ◽  
Median Eminence ◽  
Nucleus Tractus Solitarius ◽  
Acute Hypoxia ◽  
Ventrolateral Medulla ◽  
Specific Cell ◽  
External Zone ◽  
Cell Phenotypes

Hypoxia results in decreased arterial Po2, arterial chemoreflex activation, and compensatory increases in breathing, sympathetic outflow, and neuroendocrine secretions, including increased secretion of AVP, corticotropin-releasing hormone (CRH), adrenocorticotropin hormone (ACTH), and corticosterone. In addition to a brain stem pathway, including the nucleus tractus solitarius (nTS) and the rostral ventrolateral medulla (RVLM), medullary pathways to the paraventricular nucleus of the hypothalamus (PVN) contribute to chemoreflex responses. Experiments evaluated activation of specific cell phenotypes within the PVN following an acute hypoxic stimulus (AH; 2 h, 10% O2) in conscious rats. Retrograde tracers (from spinal cord and RVLM) labeled presympathetic (PreS) neurons, and immunohistochemistry identified AVP- and CRH-immunoreactive (IR) cells. c-Fos-IR was an index of neuronal activation. Hypoxia activated AVP-IR (~6%) and CRH-IR (~15%) cells, but not PreS cells in the PVN, suggesting that sympathoexcitation during moderate AH is mediated mainly by a pathway that does not include PreS neurons in the PVN. Approximately 14 to 17% of all PVN cell phenotypes examined expressed neuronal nitric oxide synthase (nNOS-IR). AH activated only nNOS-negative AVP-IR neurons. In contrast ~23% of activated CRH-IR neurons in the PVN contained nNOS. In the median eminence, CRH-IR terminals were closely opposed to tanycyte processes and end-feet (vimentin-IR) in the external zone, where vascular NO participates in tanycyte retraction to facilitate neuropeptide secretion into the pituitary portal circulation. Results are consistent with an inhibitory role of NO on AVP and PreS neurons in the PVN and an excitatory role of NO on CRH secretion in the PVN and median eminence.

Leukocyte adherence inhibits adenosine-dependent venular control of arteriolar diameter and nitric oxide

2006 ◽  
Vol 291 (2) ◽  
pp. H724-H731 ◽  
Author(s):  
Min-ho Kim ◽  
Norman R. Harris
Keyword(s):  
Nitric Oxide ◽  
Adenosine Deaminase ◽  
Intravital Microscopy ◽  
Leukocyte Adherence ◽  
Rat Mesentery ◽  
High Adherence ◽  
Local Superfusion ◽  
Arteriolar Diameter ◽  
Adherence Group ◽  
Dependent Mechanism

Venular control of arteriolar perfusion has been the focus of several investigations in recent years. This study investigated 1) whether endogenous adenosine helps control venule-dependent arteriolar dilation and 2) whether venular leukocyte adherence limits this response via an oxidant-dependent mechanism in which nitric oxide (NO) levels are decreased. Intravital microscopy was used to assess changes in arteriolar diameters and NO levels in rat mesentery. The average resting diameter of arterioles (27.5 ± 1.0 μm) paired with venules with minimal leukocyte adherence (2.1 ± 0.3 per 100-μm length) was significantly larger than that of unpaired arterioles (24.5 ± 0.8 μm) and arterioles (23.3 ± 1.3 μm) paired with venules with higher leukocyte adherence (9.0 ± 0.5 per 100-μm length). Local superfusion of adenosine deaminase (ADA) induced significant decreases in diameter and perivascular NO concentration in arterioles closely paired to venules with minimal leukocyte adherence. However, ADA had little effect on arterioles closely paired to venules with high leukocyte adherence or on unpaired arterioles. To determine whether the attenuated response to ADA for the high-adherence group was oxidant dependent, the responses were also observed in arterioles treated with 10−4 M Tempol. In the high-adherence group, Tempol fully restored NO levels to those of the low-adherence group; however, the ADA-induced constriction remained attenuated, suggesting a possible role for an oxidant-independent vasoconstrictor released from the inflamed venules. These findings suggest that adenosine- and venule-dependent dilation of paired arterioles may be mediated, in part, by NO and inhibited by venular leukocyte adherence.

Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils

1997 ◽  
Vol 273 (6) ◽  
pp. G1246-G1251 ◽  
Author(s):  
John L. Wallace ◽  
Webb McKnight ◽  
Tammy L. Wilson ◽  
Piero Del Soldato ◽  
Giuseppe Cirino
Keyword(s):  
Nitric Oxide ◽  
Hemorrhagic Shock ◽  
Gastric Damage ◽  
Leukocyte Adherence ◽  
Inhibitory Effects ◽  
Neutrophil Adherence ◽  
Nitric Oxide Releasing ◽  
Derivatives Of ◽  
Ncx 4016

The gastric damage associated with hemorrhagic shock appears to occur, at least in part, through neutrophil-dependent mechanisms. Nitric oxide (NO)-releasing derivatives of aspirin have been shown to spare the gastrointestinal tract of injury. As NO can inhibit neutrophil adherence, it is possible that such a derivative of aspirin (NCX-4016) would exert inhibitory effects on neutrophil adherence and therefore be capable of protecting the stomach against shock-induced gastric damage. This hypothesis was tested in this study. Oral administration of NCX-4016 or glyceryl trinitrate or depletion of circulating neutrophils with antineutrophil serum significantly reduced the extent of gastric damage induced by hemorrhagic shock, whereas aspirin had no effect. NCX-4016 and antineutrophil serum pretreatment resulted in significant preservation of gastric blood flow during the shock period. Moreover, NCX-4016, but not aspirin, was capable of inhibiting N-formyl-Met-Leu-Phe-induced leukocyte adherence to postcapillary mesenteric venules. These results suggest that an NO-releasing aspirin derivative reduces the susceptibility of the stomach to shock-induced damage through inhibitory effects on neutrophil adherence to the vascular endothelium.

Leukocyte adhesion induced by inhibition of nitric oxide production in skeletal muscle

1995 ◽  
Vol 78 (5) ◽  
pp. 1725-1732 ◽  
Author(s):  
T. Akimitsu ◽  
D. C. Gute ◽  
R. J. Korthuis
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Superoxide Dismutase ◽  
Leukocyte Adhesion ◽  
No Synthase ◽  
Nitric Oxide Production ◽  
Leukocyte Adherence ◽  
Synthase Inhibitor ◽  
Dependent Mechanism ◽  
Exogenous Source

Superfusion of rat cremaster muscles with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) elicited significant leukocyte adhesion to postcapillary venules (20- to 30-microns diameter), an effect that was attenuated by pretreatment with L-arginine (an NO precursor) or sodium nitroprusside (SNP) (an exogenous source of NO). In contrast to the effects of pretreatment, addition of SNP or L-arginine to the superfusate 30 min after the initiation of NO synthase inhibition failed to reverse the L-NAME-induced leukocyte adherence. However, this effect was reversed by administration of an anti-CD18 monoclonal antibody or 8-bromoguanosine 3′,5′-cyclic monophosphate 30 min after L-NAME superfusion was initiated. These findings indicate that L-NAME promotes leukocyte adhesion to venular endothelium by a CD18-dependent mechanism in skeletal muscle and suggest that the failure of L-arginine or SNP to reverse L-NAME-induced leukocyte adherence is not due to a defect in signaling events that occur subsequent to activation of guanylate cyclase by NO derived from these agents. Because the simultaneous administration of superoxide dismutase (scavenges superoxide radicals) and SNP or L-arginine, but not superoxide dismutase alone, decreased L-NAME-induced leukocyte adherence, our results suggest that leukocyte adhesion caused by NO synthase inhibition may result in the generation of superoxide.

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