Prevention of Mast Cell Degranulation by Disodium Cromoglycate Attenuates the Development of Hypoxic Pulmonary Hypertension in Rats Exposed to Chronic Hypoxia

Respiration ◽  
2008 ◽  
Vol 76 (1) ◽  
pp. 102-107 ◽  
Author(s):  
Alena Baňasová ◽  
Hana Maxová ◽  
Václav Hampl ◽  
Martin Vízek ◽  
Viera Povýšilová ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mast Cell ◽  
Chronic Hypoxia ◽  
Mast Cell Degranulation ◽  
Disodium Cromoglycate ◽  
Hypoxic Pulmonary Hypertension

scholarly journals Prevention of Mast Cell Degranulation by Disodium Cromoglycate Delayed the Regression of Hypoxic Pulmonary Hypertension in Rats

Respiration ◽  
2010 ◽  
Vol 80 (4) ◽  
pp. 335-339 ◽  
Author(s):  
Hana Maxová ◽  
Marianna Vasiľková ◽  
Jana Novotná ◽  
Olga Vajnerová ◽  
Alena Baňsová ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mast Cell ◽  
Mast Cell Degranulation ◽  
Disodium Cromoglycate ◽  
Hypoxic Pulmonary Hypertension

Chronic EDRF inhibition and hypoxia: effects on pulmonary circulation and systemic blood pressure

1993 ◽  
Vol 75 (4) ◽  
pp. 1748-1757 ◽  
Author(s):  
V. Hampl ◽  
S. L. Archer ◽  
D. P. Nelson ◽  
E. K. Weir
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Systemic Blood Pressure ◽  
Systemic Circulation ◽  
Systemic Arterial Pressure ◽  
Hypoxic Pulmonary Hypertension ◽  
Basal Tone ◽  
Isolated Lungs

It has been suggested that chronic hypoxic pulmonary hypertension results from chronic hypoxic inhibition of endothelium-derived relaxing factor (EDRF) synthesis. We tested this hypothesis by studying whether chronic EDRF inhibition by N omega-nitro-L-arginine methyl ester (L-NAME) would induce pulmonary hypertension similar to that found in chronic hypoxia. L-NAME (1.85 mM) was given for 3 wk in drinking water to rats living in normoxia or hypoxia. Unlike chronic hypoxia, chronic L-NAME treatment did not increase pulmonary arterial pressure. Cardiac output was reduced and mean systemic arterial pressure was increased by chronic L-NAME treatment. The vascular pressure-flow relationship in isolated lungs was shifted toward higher pressures by chronic hypoxia and, to a lesser degree, by L-NAME intake. In isolated lungs, vasoconstriction in response to angiotensin II and acute hypoxia and vasodilation in response to sodium nitroprusside were increased by chronic L-NAME treatment in normoxia and chronic hypoxia. Chronic hypoxia, but not L-NAME, induced hypertensive pulmonary vascular remodeling. Chronic supplementation with the EDRF precursor L-arginine did not have any significant effect on chronic hypoxic pulmonary hypertension. We conclude that the chronic EDRF deficiency state, induced by L-NAME, does not mimic chronic hypoxic pulmonary hypertension in our model. In addition, EDRF proved to be less important for basal tone regulation in the pulmonary than in the systemic circulation.

scholarly journals Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

Reproduction ◽  
2004 ◽  
Vol 127 (3) ◽  
pp. 379-387 ◽  
Author(s):  
J Varayoud ◽  
J G Ramos ◽  
V L Bosquiazzo ◽  
M Muñoz-de-Toro ◽  
E H Luque
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Blood Vessels ◽  
Uterine Cervix ◽  
Vascular System ◽  
Mast Cell Degranulation ◽  
Endothelial Cell Proliferation ◽  
Disodium Cromoglycate ◽  
Mast Cell Stabilizer ◽  
Vascular Area

During pregnancy, it is essential that sufficient nutrients are supplied by the vascular system to support the dramatic modifications of the rat uterine cervix. Angiogenesis refers to the growth of new blood vessels from pre-existing microcirculation and mast cells have been associated with this process. This study examined the modifications of the vascular compartment and the distribution of mast cells on cervical tissue during pregnancy. Using disodium cromoglycate as a mast cell stabilizer, we determined the effects of the mast cell degranulation on cervical angiogenesis. Mast cell distribution and their degranulation status were evaluated by immunohistochemistry. Endothelial cell proliferation was measured by bromodeoxyuridine incorporation. Vascular areas (absolute and relative) and maturation indices were assessed by quantitative immunohistochemistry of von Willebrand factor and α-smooth muscle actin respectively. Mast cells were predominantly observed during the first half of pregnancy in the perivascular zones. The values of bromodeoxyuridine incorporation, absolute vascular area and vascular maturation index exhibited a significant increase throughout pregnancy. All animals that received mast cell stabilizer showed more than 40% of non-degranulated mast cells. Treated rats exhibited a decrease in endothelial proliferation and in relative vascular area; in addition, a large proportion of mature blood vessels was observed, suggesting a diminished level of new vessel formation. The effects of the mast cell stabilizer were sustained beyond the end of treatment. This is the first report that brings evidence that mast cell degranulation could be a necessary process to contribute to the normal angiogenesis of the rat cervix during pregnancy. Further investigations are needed to elucidate the possible implications of abnormal vascular development of the uterine cervix on the physiological process of ripening and parturition.

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

2002 ◽  
Vol 283 (2) ◽  
pp. H733-H740 ◽  
Author(s):  
Christophe Adamy ◽  
Patricia Oliviero ◽  
Saadia Eddahibi ◽  
Lydie Rappaport ◽  
Jane-Lise Samuel ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Chronic Hypoxia ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Hypoxic Pulmonary Hypertension ◽  
Cardiac Ventricles ◽  
The Right

Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT1 and AT2expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase ( P < 0.05) in AT1 binding and AT1 mRNA levels in the absence of any significant change in AT2 expression level. Only after 14 days of hypoxia, AT2 binding increased ( P < 0.05) in the two ventricles, concomitantly with a right ventricular decrease ( P < 0.05) in AT2 mRNA. Along these data, AT1 and AT2 binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT1 and AT2 receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia.

Cellular adaptation during chronic neonatal hypoxic pulmonary hypertension

1991 ◽  
Vol 261 (4) ◽  
pp. L97-L104 ◽  
Author(s):  
Kurt R. Stenmark ◽  
Almas A. Aldashev ◽  
Ernest C. Orton ◽  
A. G. Durmowicz ◽  
D. B. Badesch ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Arterial Wall ◽  
Chronic Hypoxia ◽  
Left Pulmonary Artery ◽  
Right Atrial ◽  
Vascular Changes ◽  
Hypoxic Pulmonary Hypertension

Newbor animals develop more severe hypoxic pulmonary hypertension than do adults, their vascular changes are greater, and both the hypertension and vascular changes occur more rapidly. We hypothesize that this differential developmentally controlled response may arise from either a difference in the type or quantity of endogenously secreted mediators in response to a given injury or a difference in the replicative and/or matrix-producing response of the vascular cells to physical or chemical stimuli. We investigated the effect of chronic hypoxia (14 days) on the proliferative and matrix-producing phenotype of the neonatal (14-day-old) pulmonary artery smooth muscle cell (SMC) and examined the heterogeneity and potential mechanisms responsible for this response. In situ hybridization studies demonstrated a remarkable change in the distribution of cells hybridizing with a tropoelastin cRNA probe after 14 days of hypoxia. Studies also demonstrated a population of SMC that did not hybridize with the elastin or collagen probes, indicating that the pulmonary artery contains SMC of multiple phenotypes and that the response to hypoxic and hemodynamic stress is not uniform for the various types. Bromodeoxyuridine labeling experiments indicated a large increase in DNA synthesis in hypertensive vessels, which, again, was not uniform either across or along the arterial wall. In vitro experiments with neonatal SMC suggested that hypoxia alone could not be responsible for the proliferative or matrix changes. These observations were supported by in vivo experiments in which coarctation of the left pulmonary artery, which markedly decreased pressure and flow to the left lung in hypoxic animals (14 days), resulted in significant decreases in collagen and elastin message levels in the left pulmonary artery distal to the coarctation compared with location-matched vessels from the right lung. Finally, we noted marked decreases in B-receptor density and adenyl cyclase activity in right atrial and pulmonary artery tissue from the chronically hypoxic animals. Decreases in the ability of the cell to produce adenosine 3',5'-cyclic monophosphate could significantly affect both the proliferative and matrix-producing potential of the SMC. We conclude that in vivo adaptation of the pulmonary artery SMC to chronic hypoxia includes changes in protein synthesis, cell proliferation, receptor expression, and enzyme activity. Further, there is a marked heterogeneity of these responses both across and along the arterial wall. hypoxia; phenotype; signal transductions; smooth muscle cells

N-acetylcysteine inhibits hypoxic pulmonary hypertension most effectively in the initial phase of chronic hypoxia

Life Sciences ◽  
2005 ◽  
Vol 77 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Věra Lachmanová ◽  
Olga Hniličková ◽  
Viera Povýšilová ◽  
Václav Hampl ◽  
Jan Herget
Keyword(s):  
Pulmonary Hypertension ◽  
Initial Phase ◽  
Chronic Hypoxia ◽  
Hypoxic Pulmonary Hypertension

Hypoxic pulmonary hypertension is prevented in rats with common bile duct ligation

2005 ◽  
Vol 98 (2) ◽  
pp. 739-747 ◽  
Author(s):  
Masatoshi Imamura ◽  
Bao Luo ◽  
Jennifer Limbird ◽  
Andrea Vitello ◽  
Masahiko Oka ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Liver Cirrhosis ◽  
Bile Duct ◽  
Chronic Hypoxia ◽  
Bile Duct Ligation ◽  
Heme Oxygenase 1 ◽  
Common Bile Duct Ligation ◽  
Hypoxic Pulmonary Hypertension ◽  
Vascular Responses ◽  
Duct Ligation

Biliary cirrhosis in the rat triggers intrapulmonary vasodilatation and gas-exchange abnormalities that characterize the hepatopulmonary syndrome. This vasodilatation correlates with increased levels of pulmonary microcirculatory endothelial NO synthase (eNOS) and hepatic and plasma endothelin-1 (ET-1). Importantly, during cirrhosis, the pulmonary vascular responses to acute hypoxia are blunted. The purpose of this work was to examine the pulmonary vascular responses and adaptations to the combination of liver cirrhosis and chronic hypoxia (CH). In addition to hemodynamic measurements, we investigated whether pulmonary expression changes of eNOS, ET-1 and its receptors (endothelin A and B), or heme oxygenase 1 in experimental cirrhosis affect the development of hypoxic pulmonary hypertension. We induced cirrhosis in male Sprague-Dawley rats using common bile duct ligation (CBDL) and exposed them to CH (inspired Po2 ≈ 76 Torr) or maintained them in Denver (Den, inspired Po2 ≈ 122 Torr) for 3 wk. Our data show 1) CBDL-CH rats had a persistent blunted hypoxic pulmonary vasoconstriction similar to CBDL-Den; 2) the development of hypoxic pulmonary hypertension was completely prevented in the CBDL-CH rats, as indicated by normal pulmonary arterial pressure and lack of right ventricular hypertrophy and pulmonary arteriole remodeling; and 3) selective increases in expression of ET-1, pulmonary endothelin B receptor, eNOS, and heme oxygenase 1 are potential mechanisms of protection against hypoxic pulmonary hypertension in the CBDL-CH rats. These data demonstrate that unique and undefined hepatic-pulmonary interactions occur during liver cirrhosis and chronic hypoxia. Understanding these interactions may provide important information for the prevention and treatment of pulmonary hypertension.

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