Endogenous nitric oxide on arterial hemodynamics: a  comparison between normotensive and hypertensive rats

Chen, Hsing I.; Hu, Cheng

doi:10.1152/ajpheart.1997.273.4.h1816

Cited by 30 publications

(42 citation statements)

References 31 publications

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“…The release of NO from L-arginine may be beneficial in certain conditions, but it becomes toxic in other situations [5,7,24,25]. Chen and Hu [6] reported that the basal function of NO was enhanced in the spontaneously hypertensive rat (SHR) compared to the normotensive Wistar-Kyoto strain (WKY).…”

Section: Discussionmentioning

confidence: 99%

“…The NOS in endothelial cells (eNOS) and neuronal cells (nNOS) are expressed mainly constitutively and their activity is Ca 2+ dependent. Under physiological conditions, the release of NO by eNOS causes vasodilatation and regulates blood flow as well as blood pressure [5,7,16,25]. Another inducible NOS (iNOS) is Ca 2÷ independent and can be induced by immunological stimuli such as endotoxins or cytokines in phagocytic cells (macrophages, leukocytes) [10,21,24].…”

Section: Introductionmentioning

confidence: 99%

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Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats

et al. 1999

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Endotoxin shock is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors and acute lung edema. A nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA) has been shown to be effective in reversing acute lung injury. In the present study, we evaluated the effects of NOS blockade by different mechanisms on the endotoxin-induced changes. In anesthetized rats, lipopolysaccharide (LPS, Klebsiella pneumoniae) was administered intravenously in a dose of 10 mg/kg. LPS caused sustained systemic hypotension accompanied by an eightfold increase of exhaled NO during an observation period of 4 h. After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expressions of inducible NOS (iNOS), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha-(TNF-alpha). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1beta and TNF-alpha were absent. Four hours after LPS, the mRNA expressions of iNOS and IL-1beta were still significantly enhanced, but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial damage and interstitial edema. Various NOS inhibitors were given 1 h after LPS administration. These agents included Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), a constitutive NOS and iNOS inhibitor; S, S'-1,4-phenylene-bis-(1,2-ethanedinyl) bis-isothiourea dihydrobromide (1,4-PBIT, 10 mg/kg), a relatively specific iNOS inhibitor, and dexamethasone (3 mg/kg), an inhibitor of iNOS expression. These NOS inhibitors all effectively reversed the systemic hypotension, reduced the exhaled NO concentration and prevented acute lung injury. The LPS-induced mRNA expressions of iNOS and IL-1beta were also significantly depressed by these NOS inhibitors. Our results suggest that NO production through the iNOS pathway is responsible for endotoxin-induced lung injury. Certain cytokines such as IL-1beta are possibly involved. These changes are minimized by NOS inhibitors through different mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats

et al. 1999

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“…It was likely that TNF-· was a sensitive and early cytokine after the endotoxin, whereas IL-1ß was induced later and was relatively longer lasting. The release of NO from L-arginine may be beneficial in certain conditions, but it becomes toxic in other situations [5,7,24,25]. Chen and Hu [6] reported that the basal function of NO was enhanced in the spontaneously hypertensive rat (SHR) compared to the normotensive Wistar-Kyoto strain (WKY).…”

Section: Discussionmentioning

confidence: 99%

Effects of Nitric Oxide Synthase Inhibitors on Systemic Hypotension, Cytokines and Inducible Nitric Oxide Synthase Expression and Lung Injury following Endotoxin Administration in Rats

et al. 1999

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Endotoxin shock is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors and acute lung edema. A nitric oxide synthase (NOS) inhibitor, N^G-monomethyl-L-arginine (L-NMMA) has been shown to be effective in reversing acute lung injury. In the present study, we evaluated the effects of NOS blockade by different mechanisms on the endotoxin-induced changes. In anesthetized rats, lipopolysaccharide (LPS, Klebsiella pneumoniae) was administered intravenously in a dose of 10 mg/kg. LPS caused sustained systemic hypotension accompanied by an eightfold increase of exhaled NO during an observation period of 4 h. After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expressions of inducible NOS (iNOS), interleukin-1β (IL-1β) and tumor necrosis factor-α-(TNF-α). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1β and TNF-α were absent. Four hours after LPS, the mRNA expressions of iNOS and IL-1β were still significantly enhanced, but TNF-α was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial damage and interstitial edema. Various NOS inhibitors were given 1 h after LPS administration. These agents included N^ω-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), a constitutive NOS and iNOS inhibitor; S,S′-1,4-phenylene-bis-(1,2-ethanedinyl) bis-isothiourea dihydrobromide (1,4-PBIT, 10 mg/kg), a relatively specific iNOS inhibitor, and dexamethasone (3 mg/kg), an inhibitor of iNOS expression. These NOS inhibitors all effectively reversed the systemic hypotension, reduced the exhaled NO concentration and prevented acute lung injury. The LPS-induced mRNA expressions of iNOS and IL-1β were also significantly depressed by these NOS inhibitors. Our results suggest that NO production through the iNOS pathway is responsible for endotoxin-induced lung injury. Certain cytokines such as IL-1β are possibly involved. These changes are minimized by NOS inhibitors through different mechanisms.

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“…NO is an important substance in the regulation of arterial pressure [5,6,20,27,30]. Since NO is a free radical, however, it may lead to the formation of hydroxyl radical and peroxynitrite, which are toxic to many organs including the lung [27,33,38].…”

Section: Chemical Factors and Involvement Of Nomentioning

confidence: 99%

Acute Respiratory Distress Syndrome

Chen

Kao²,

Wang

et al. 2003

J Biomed Sci

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Acute respiratory distress syndrome (ARDS) can be associated with various disorders. Among these, coronavirus infection may cause life-threatening severe acute respiratory syndrome (SARS). In this review, we present animal models and techniques for the study of ARDS, and discuss the roles and possible mechanisms of various chemical factors, including nitric oxide (NO). Our early work revealed that cerebral compression elicits severe hemorrhagic pulmonary edema (PE), leading to central sympathetic activation that results in systemic vasoconstriction. The consequence of systemic vasoconstriction is volume and pressure loading in the pulmonary circulation. Vasodilators, but not oxidant radical scavengers, are effective in the prevention of centrogenic PE. In isolated perfused lung, exogenous and endogenous NO enhances lung injury following air embolism and ischemia/reperfusion. In contrast, NO synthase (NOS) inhibitors reverse such lung injury. Although NO is important in maintaining vasodilator tone, hypoxia-induced pulmonary vasoconstriction is accompanied by an increase instead of a decrease in NO release. In animal and isolated lung studies, endotoxin produces acute lung injury that is associated with increases in cytokines and inducible NOS mRNA expression, suggesting that NO is toxic to the lung in endotoxin shock. Recently, we reported several rare cases that indicate that ARDS in patients with Japanese B encephalitis, lymphangitis with breast cancer and fat embolism is caused by different mechanisms. Our early and recent studies on ARDS and PE may provide information for clinical practice and the understanding of the pathogenesis of SARS.

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Endogenous nitric oxide on arterial hemodynamics: a comparison between normotensive and hypertensive rats

Cited by 30 publications

References 31 publications

Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats

Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats

Effects of Nitric Oxide Synthase Inhibitors on Systemic Hypotension, Cytokines and Inducible Nitric Oxide Synthase Expression and Lung Injury following Endotoxin Administration in Rats

Acute Respiratory Distress Syndrome

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