Pulmonary Endothelium and Nitric Oxide

2009 ◽  
pp. 89-104
Author(s):  
Yunchao Su ◽  
Edward R. Block
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Endothelium

Prevention of ischemia-reperfusion lung injury by inhaled nitric oxide in neonatal piglets

1996 ◽  
Vol 80 (3) ◽  
pp. 782-788 ◽  
Author(s):  
F. Barbotin-Larrieu ◽  
M. Mazmanian ◽  
B. Baudet ◽  
H. Detruit ◽  
A. Chapelier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Neutrophil Accumulation ◽  
Pulmonary Endothelium ◽  
Neonatal Piglets ◽  
Neonatal Piglet ◽  
Pulmonary Arterial ◽  
Coefficient Of Filtration

Lung ischemia-reperfusion results in a decrease in the release of nitric oxide (NO) by the pulmonary endothelium. NO may have lung-protective effects by decreasing neutrophil accumulation in the lung. We tested whether NO inhalation would attenuate reperfusion-induced endothelial dysfunction and increases in microvascular permeability and total pulmonary vascular resistance (RT) by preventing neutrophil lung accumulation. After baseline determinations of RT, coefficient of filtration (Kfc), and circulating neutrophil counts, isolated neonatal piglet lungs were subjected to a 1-h period of ischemia followed by a 1-h period of blood reperfusion and reventilation with or without addition of NO (10 ppm). NO prevented reperfusion-induced increases in RT and Kfc, as well as the decrease in circulating neutrophils. After reperfusion, increases in Kfc were correlated with decreases in circulating neutrophils. NO prevented reperfusion-induced decrease in endothelium-dependent relaxation in precontracted pulmonary arterial rings. This demonstrates that inhaled NO prevents microvascular injury, endothelial dysfunction, and pulmonary neutrophil accumulation in a neonatal piglet model of lung ischemia-reperfusion.

scholarly journals Nitric oxide and pulmonary arterial hypertension

2017 ◽  
Vol 2017 (2) ◽  
Author(s):  
Adrian H Chester ◽  
Magdi H Yacoub ◽  
Salvador Moncada
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Tone ◽  
Pathological Changes ◽  
Pulmonary Endothelium ◽  
Physiological Conditions ◽  
Vasoactive Factors ◽  
Pulmonary Arterial

The pathogenesis of pulmonary arterial hypertension remains undefined. Changes in the expression and effects mediated by a number of vasoactive factors have been implicated to play a role in the onset and progression of the disease. The source of many of these mediators, such as nitric oxide (NO), prostacyclin and endothelin-1 (ET-1), is the pulmonary endothelium. This article focus in the role of nitric oxide in PAH, reviewing the evidence for its involvement in regulation of pulmonary a vascular tone under physiological conditions, the mechanisms by which it can contribute to the pathological changes seen in PAH and strategies for the use of NO as a therapy for treatment of the disease. 

scholarly journals Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth

2016 ◽  
Vol 310 (3) ◽  
pp. L271-L286 ◽  
Author(s):  
Carla Blum-Johnston ◽  
Richard B. Thorpe ◽  
Chelsea Wee ◽  
Monica Romero ◽  
Alexander Brunelle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Hypoxia ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Fetal Sheep ◽  
Pulmonary Endothelium ◽  
Channel Inhibition ◽  
Subunit Expression ◽  
Intracellular Ca ◽  
Near Term

Bradykinin-induced activation of the pulmonary endothelium triggers nitric oxide production and other signals that cause vasorelaxation, including stimulation of large-conductance Ca2+-activated K+ (BKCa) channels in myocytes that hyperpolarize the plasma membrane and decrease intracellular Ca2+. Intrauterine chronic hypoxia (CH) may reduce vasorelaxation in the fetal-to-newborn transition and contribute to pulmonary hypertension of the newborn. Thus we examined the effects of maturation and CH on the role of BKCa channels during bradykinin-induced vasorelaxation by examining endothelial Ca2+ signals, wire myography, and Western immunoblots on pulmonary arteries isolated from near-term fetal (∼140 days gestation) and newborn, 10- to 20-day-old, sheep that lived in normoxia at 700 m or in CH at high altitude (3,801 m) for >100 days. CH enhanced bradykinin-induced relaxation of fetal vessels but decreased relaxation in newborns. Endothelial Ca2+ responses decreased with maturation but increased with CH. Bradykinin-dependent relaxation was sensitive to 100 μM nitro-l-arginine methyl ester or 10 μM 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one, supporting roles for endothelial nitric oxide synthase and soluble guanylate cyclase activation. Indomethacin blocked relaxation in CH vessels, suggesting upregulation of PLA2 pathways. BKCa channel inhibition with 1 mM tetraethylammonium reduced bradykinin-induced vasorelaxation in the normoxic newborn and fetal CH vessels. Maturation reduced whole cell BKCa channel α1-subunit expression but increased β1-subunit expression. These results suggest that CH amplifies the contribution of BKCa channels to bradykinin-induced vasorelaxation in fetal sheep but stunts further development of this vasodilatory pathway in newborns. This involves complex changes in multiple components of the bradykinin-signaling axes.

scholarly journals Nitric‐oxide, zinc and hypoxia‐induced contraction of isolated pulmonary endothelium

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Claudette Marie St. Croix ◽  
Karanee Leelavanichkul ◽  
Bruce R Pitt ◽  
Frederick Lanni ◽  
Simon C Watkins
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Endothelium

Nitric oxide and zinc homeostasis in pulmonary endothelium

2010 ◽  
Vol 1203 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Huihua Li ◽  
Rong Cao ◽  
Karla J. Wasserloos ◽  
Paula Bernal ◽  
Zhao-Qian Liu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Zinc Homeostasis ◽  
Pulmonary Endothelium

scholarly journals Angiotensin II-Stimulated Nitric Oxide Release from Porcine Pulmonary Endothelium Is Mediated by Angiotensin IV

1999 ◽  
Vol 10 (3) ◽  
pp. 481-491
Author(s):  
NATHALIE HILL-KAPTURCZAK ◽  
MATTHIAS H. KAPTURCZAK ◽  
EDWARD R. BLOCK ◽  
JAWAHARLAL M. PATEL ◽  
TADEUSZ MALINSKI ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Angiotensin Iv ◽  
Pulmonary Endothelium ◽  
Nitric Oxide Release ◽  
Receptor Inhibition ◽  
No Release ◽  
Vascular Beds ◽  
No Sensor ◽  
Porcine Pulmonary Artery

Abstract. In this study, a nitric oxide (NO) sensor was used to examine the ability of angiotensin II (AngII), AngIV, and bradykinin (Bk) to stimulate NO release from porcine pulmonary artery (PPAE) and porcine aortic endothelial (PAE) cells and to explore the mechanism of the AngII-stimulated NO release. Physiologic concentrations of AngII, but not Bk, caused release of NO from PPAE cells. In contrast, Bk, but not AngII, stimulated NO release from PAE cells. AngII-stimulated NO release from PPAE cells required extracellular L-arginine and was inhibited by L-nitro-arginine methyl ester. AT1 and AT2 receptor inhibition had no affect on AngII-mediated NO release or activation of NO synthase (NOS). AngIV, and AngII metabolite with binding sites that are pharmacologically distinct from the classic AngII receptors, stimulated considerably greater NO release and greater endothelial-type constitutive NOS activity than the same amount of AngII. The AngIV receptor antagonist, divalinal AngIV, blocked both AngII- and AngIV-mediated NO release as well as NOS activation. The results demonstrate that AngIV and the AngIV receptor are responsible, at least in part, for AngII-stimulated NO release and the associated endothelium-dependent vasorelaxation. Furthermore, these results suggest that differences exist in both AngII- and Bk-mediated NO release between PPAE and PAE cells, which may reflect important differences in response to these hormones between vascular beds.

scholarly journals Long-term hypoxia uncouples Ca2+ and eNOS in bradykinin-mediated pulmonary arterial relaxation

2018 ◽  
Vol 314 (6) ◽  
pp. R870-R882 ◽  
Author(s):  
Carla Blum-Johnston ◽  
Richard B. Thorpe ◽  
Chelsea Wee ◽  
Raechel Opsahl ◽  
Monica Romero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
High Altitude ◽  
Pulmonary Arteries ◽  
Α Subunit ◽  
Pulmonary Endothelium ◽  
Subunit Expression ◽  
Intracellular Ca ◽  
Pulmonary Arterial ◽  
Endothelial Nitric Oxide

Bradykinin-induced activation of the pulmonary endothelium triggers a rise in intracellular Ca2+ that activates nitric oxide (NO)-dependent vasorelaxation. Chronic hypoxia is commonly associated with increased pulmonary vascular tone, which can cause pulmonary hypertension in responsive individuals. In the present study, we tested the hypothesis that long-term high-altitude hypoxia (LTH) diminishes bradykinin-induced Ca2+ signals and inhibits endothelial nitric oxide synthase (eNOS), prostacyclin (PGI2), and large-conductance K+ (BKCa) channels in sheep, which are moderately responsive to LTH, resulting in decreased pulmonary arterial vasorelaxation. Pulmonary arteries were isolated from ewes kept near sea level (720 m) or at high altitude (3,801 m) for >100 days. Vessel force was measured with wire myography and endothelial intracellular Ca2+ with confocal microscopy. eNOS was inhibited with 100 μM NG-nitro-l-arginine methyl ester (l-NAME), PGI2 production was inhibited with 10 µM indomethacin that inhibits cyclooxygenase, and BKCa channels were blocked with 1 mM tetraethylammonium. Bradykinin-induced endothelial Ca2+ signals increased following LTH, but bradykinin relaxation decreased. Furthermore, some vessels contracted in response to bradykinin after LTH. l-NAME sensitivity decreased, suggesting that eNOS dysfunction played a role in uncoupling Ca2+ signals and bradykinin relaxation. The Ca2+ ionophore A-23187 (10 µM) elicited an enhanced Ca2+ response following LTH while relaxation was unchanged although l-NAME sensitivity increased. Additionally, BKCa function decreased during bradykinin relaxation following LTH. Western analysis showed that BKCa α-subunit expression was increased by LTH while that for the β1 subunit was unchanged. Overall, these results suggest that those even moderately responsive to LTH can have impaired endothelial function.

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