Regulation ofPulmonary Endothelial CellShape byTRP- Mediated CalciumEntry* (original) (raw)
Related papers
British Journal of Pharmacology, 2003
1 Chronic hypoxia (CH) increases lung tissue expression of all types of nitric oxide synthase (NOS) in the rat. However, it remains unknown whether CH-induced changes in functional and histological NOS distributions are correlated in rat small pulmonary arteries. 2 We measured the effects of NOS inhibitors on the internal diameters (ID) of muscular (MPA) and elastic (EPA) pulmonary arteries (100 -700 mm ID) using an X-ray television system on anaesthetized rats. We also conducted NOS immunohistochemical localization on the same vessels. 3 Nonselective NOS inhibitors induced ID reductions in almost all MPA of CH rats (mean reduction, 3673%), as compared to B60% of control rat MPA (mean, 1072%). The inhibitors reduced the ID of almost all EPA with similar mean values (B26%) in both CH and control rats. On the other hand, inducible NOS (iNOS)-selective inhibitors caused ID reductions in B60% of CH rat MPA (mean, 1573%), but did so in only B20% of control rat MPA (mean, 272%). This inhibition caused only a small reduction (mean, B4%) in both CH and control rat EPA. A neuronal NOSselective inhibitor had no effect. 4 The percentage of endothelial NOS (eNOS)-positive vessels was B96% in both MPA and EPA from CH rats, whereas it was 51 and 91% in control MPA and EPA, respectively. The percentage for iNOS was B60% in both MPA and EPA from CH rats, but was only B8% in both arteries from control rats. 5 The data indicate that in CH rats, both functional and histological upregulation of eNOS extensively occurs within MPA. iNOS protein increases sporadically among parallel-arranged branches in both MPA and EPA, but its vasodilatory effect is predominantly observed in MPA. Such NOS upregulation may serve to attenuate hypoxic vasoconstriction, which occurs primarily in MPA and inhibit the progress of pulmonary hypertension.
Lung eNOS and iNOS are Reoxygenation Time-Dependent Upregulated After Acute Hypoxia
The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 2010
Nitric oxide plays a critical role in many physiological and physiopathological processes in the lung. Changes in the NO/NOS (Nitric Oxide/ Nitric Oxide Synthase) system after hypoxia situations remain controversial in this organ, so that the aim of this work is to perform a complete study of this system in the hypoxic lung after different reoxygenation times ranging from 0 h to 5 days posthypoxia. This is a novel follow-up study carried out in Wistar rats submitted for 30 min to acute hypobaric hypoxia. We measured endothelial and inducible NOS (eNOS, iNOS) mRNA and protein expression, location, and in situ NOS activity as well as nitrated protein expression and location. In addition, NO levels were indirectly quantified (NOx) as well as the apoptosis level. Results showed an increase in eNOS mRNA, protein, activity as well as eNOS positive immunostaining at 0 h posthypoxia, coinciding with raised NOx levels. Contrary, iNOS, nitrated protein expression and apoptosis level augmented during the final reoxygenation times. The lung NO/NOS system provokes two responses to the hypoxia/reoxygenation processes: (i) eNOS is responsible of the immediate response, producing NO, which causes vasodilation and bronchodilation, and (ii) iNOS is related to the second late response, which seems to be involved in some of the deleterious consequences that hypoxia induces in the lung. Anat Rec, 293:1089-1098,
Biopterin Metabolism and eNOS Expression during Hypoxic Pulmonary Hypertension in Mice
PLoS ONE, 2013
Tetrahydrobiopterin (BH 4 ), which fosters the formation of and stabilizes endothelial NO synthase (eNOS) as an active dimer, tightly regulates eNOS coupling / uncoupling. Moreover, studies conducted in genetically-modified models demonstrate that BH 4 pulmonary deficiency is a key determinant in the pathogenesis of pulmonary hypertension. The present study thus investigates biopterin metabolism and eNOS expression, as well as the effect of sepiapterin (a precursor of BH 4 ) and eNOS gene deletion, in a mice model of hypoxic pulmonary hypertension. In lungs, chronic hypoxia increased BH 4 levels and eNOS expression, without modifying dihydrobiopterin (BH 2 , the oxidation product of BH 4 ) levels, GTP cyclohydrolase-1 or dihydrofolate reductase expression (two key enzymes regulating BH 4 availability). In intrapulmonary arteries, chronic hypoxia also increased expression of eNOS, but did not induce destabilisation of eNOS dimers into monomers. In hypoxic mice, sepiapterin prevented increase in right ventricular systolic pressure and right ventricular hypertrophy, whereas it modified neither remodelling nor alteration in vasomotor responses (hyper-responsiveness to phenylephrine, decrease in endothelium-dependent relaxation to acetylcholine) in intrapulmonary arteries. Finally, deletion of eNOS gene partially prevented hypoxia-induced increase in right ventricular systolic pressure, right ventricular hypertrophy and remodelling of intrapulmonary arteries. Collectively, these data demonstrate the absence of BH 4 /BH 2 changes and eNOS dimer destabilisation, which may induce eNOS uncoupling during hypoxia-induced pulmonary hypertension. Thus, even though eNOS gene deletion and sepiapterin treatment exert protective effects on hypoxia-induced pulmonary vascular remodelling, increase on right ventricular pressure and / or right ventricular hypertrophy, these effects appear unrelated to biopterin-dependent eNOS uncoupling within pulmonary vasculature of hypoxic wild-type mice. Citation: Dubois M, Delannoy E, Duluc L, Closs E, Li H, et al. (2013) Biopterin Metabolism and eNOS Expression during Hypoxic Pulmonary Hypertension in Mice. PLoS ONE 8(11): e82594.
Endothelial control of the pulmonary circulation in normal and chronically hypoxic rats
The Journal of physiology, 1993
1. The effect of blockade of nitric oxide synthesis in pulmonary endothelium by two L-arginine analogues was tested in isolated blood-perfused lungs of normal rats and rats exposed chronically to 10% O2. 2. In both groups of rats the analogues (N-monomethyl-L-arginine (L-NMMA) and N-nitro-L-arginine methyl ester (L-NAME)) enhanced hypoxic vasoconstriction. In normal rats, with rare exceptions, these analogues had little or no effect on pulmonary artery pressure (Ppa) at constant blood flow during normoxia. However, chronically hypoxic rats have pulmonary hypertension and in these rats the analogues always raised Ppa; the rise in Ppa after L-NMMA but not L-NAME could be partially reversed by L-arginine. L-NAME was more potent than L-NMMA. 3. To see whether the difference between rat groups was due to the high Ppa in chronically hypoxic rats, in control rats we raised Ppa passively by lung inflation to values higher than found in chronically hypoxic rats. L-NAME did not alter the effe...
eNOS-deficient mice show reduced pulmonary vascular proliferation and remodeling to chronic hypoxia
American journal of physiology. Lung cellular and molecular physiology, 2000
Pulmonary hypertension is characterized by structural and morphological changes to the lung vasculature. To determine the potential role of nitric oxide in the vascular remodeling induced by hypoxia, we exposed wild-type [WT(+/+)] and endothelial nitric oxide synthase (eNOS)-deficient [(-/-)] mice to normoxia or hypoxia (10% O(2)) for 2, 4, and 6 days or for 3 wk. Smooth muscle alpha-actin and von Willebrand factor immunohistochemistry revealed significantly less muscularization of small vessels in hypoxic eNOS(-/-) mouse lungs than in WT(+/+) mouse lungs at early time points, a finding that correlated with decreases in proliferating vascular cells (5-bromo-2'-deoxyuridine positive) at 4 and 6 days of hypoxia in the eNOS(-/-) mice. After 3 wk of hypoxia, both mouse types exhibited similar percentages of muscularized small vessels; however, only the WT(+/+) mice exhibited an increase in the percentage of fully muscularized vessels and increased vessel wall thickness. eNOS protein...
Experimental biology and medicine (Maywood, N.J.), 2006
Pulmonary hypertension (PH) usually develops secondary to left ventricular (LV) dysfunction; therefore, it is also called retrograde PH. To investigate our hypothesis that PH is at least partially reversible, as in some congenital heart diseases, in a rat model we investigated whether release of constriction could attenuate pulmonary vascular remodeling and change the expression of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS). We used rats with LV dysfunction produced by an ascending aortic banding. In this study, there were four groups enrolled: 4-weeks banded (AOB(1-28); n = 7), 7-weeks banded (AOB(1-49); n = 7), debanded groups (AOB(1-28)/DeB(29-49); n = 7), and rats receiving a sham operation (n = 7). Subsequently, there was significant attenuation of medial hypertrophy in pulmonary arterioles and reversal of PH in the AOB(1-28)/DeB(29-49) group (sham, 19 +/- 1.3 mm Hg; AOB(1-28), 31 +/- 2.7 mm Hg; AOB(1-49), 32 +/- 2.7 mm Hg; and AOB(1-28)/DeB(29-49), 20 +/- 1...
American Journal ofPhysiology: Lung Cellular and Molecular Physiology
22 other HighWire hosted articles, the first 5 are: This article has been cited by [PDF] [Full Text] [Abstract] , November 1, 2003; 285 (5): L1006-L1017. Am J Physiol Lung Cell Mol Physiol Role of Ca2+ in diperoxovanadate-induced cytoskeletal remodeling and endothelial cell [PDF] [Full Text] [Abstract] , February 1, 2004; 286 (2): L445-L451. Role of EETs in regulation of endothelial permeability in rat lung [PDF] [Full Text] [Abstract] , February 1, 2004; 286 (2): L231-L246. Evaluation of lung injury in rats and mice [PDF] [Full Text] [Abstract] , May 1, 2005; 288 (5): L849-L859. Direct ANP inhibition of hypoxia-induced inflammatory pathways in pulmonary [PDF] [Full Text] [Abstract] , March 1, 2007; 292 (3): L671-L677. Am J Physiol Lung Cell Mol Physiol V. Solodushko and B. Fouty Proproliferative phenotype of pulmonary microvascular endothelial cells on the following topics: http://highwire.stanford.edu/lists/artbytopic.dtl can be found at Medline items on this article's topics Physiology .. Rats Physiology .. Lungs Physiology .. Microvasculature Physiology .. Microcirculation Medicine .. Edema Cell Biology .. Endothelial Cells including high-resolution figures, can be found at: Updated information and services http://ajplung.physiology.org/cgi/content/full/276/1/L41 at: can be found AJP -Lung Cellular and Molecular Physiology about Additional material and information http://www.the-aps.org/publications/ajplung This information is current as of October 22, 2007 . integrative aspects of normal and abnormal function of cells and components of the respiratory system. It is published 12 times a year publishes original research covering the broad scope of molecular, cellular, and AJP -Lung Cellular and Molecular Physiology on October 22, 2007 ajplung.physiology.org Downloaded from
Endothelium-derived mediators and hypoxic pulmonary vasoconstriction
Respiratory Physiology & Neurobiology, 2002
The vascular endothelium synthesises, metabolises or converts a multitude of vasoactive mediators, and plays a vital role in the regulation of pulmonary vascular resistance. Its role in hypoxic pulmonary vasoconstriction (HPV) is however controversial. Although HPV has been demonstrated in both pulmonary arteries where the endothelium has been removed and isolated pulmonary artery smooth muscle cells, many reports have shown either partial or complete dependence on an intact endothelium for sustained HPV (\ 20 min). However, despite many years of study no known endothelium-derived mediator has yet been unequivocally shown to be essential for HPV, although several may either facilitate the response or act as physiological brakes to limit the extent of HPV. In this article we review the evidence for and against the role of specific endothelium-derived mediators in HPV. We make the case for a facilitatory or permissive function of the endothelium, that in conjunction with a rise in smooth muscle intracellular Ca 2 + initiated by a mechanism intrinsic to smooth muscle, allows the development of sustained HPV. In particular, we propose that in response to hypoxia the pulmonary vascular endothelium releases an as yet unidentified agent that causes Ca 2 + sensitisation in the smooth muscle.