Hypoxia and lung mast cells: influence of disodium cromoglycate.

Mungall, I. P. F.

doi:10.1136/thx.31.1.94

Cited by 29 publications

(22 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study has confirmed the observations of Kay et al (1974), Mungall and and Mungall (1976) that a hyperplasia of mast cells occurs around the pulmonary blood vessels and within the alveolar walls of rats exposed to chronic hypoxia, and that the intensity of the mast cell hyperplasia is related to the degree of right ventricular hypertrophy. However, these observations have been extended by the present investigation which has revealed that the hyperplasia of mast cells in the lung is reversible once the hypoxic stimulus has been removed.…”

Section: Discussionsupporting

confidence: 80%

“…Mungall (1976) showed that in chronically hypoxic rats, the mast cells did not proliferate until after 21 days of exposure, whereas right ventricular hypertrophy was apparent after only 14 days. The fact that right ventricular hypertrophy apparently precedes lung mast cell hyperplasia makes it unlikely that it is lung mast cell hyperplasia which causes the pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure of rats to chronic hypoxia for three weeks has been reported as leading to a proliferation of mast cells around small pulmonary blood vessels and within the alveolar walls (Kay et al, 1974;Mungall and Barer, 1975;Mungall, 1976). The magnitude of the mast cell hyperplasia correlates with the degree of right ventricular hypertrophy, suggesting that in the rat pulmonary mast cells may be connected in some way with chronic hypoxic pulmonary hypertension.…”

mentioning

confidence: 96%

See 2 more Smart Citations

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

Williams¹,

Heath²,

Kày³

et al. 1977

Thorax

View full text Add to dashboard Cite

(1977). Thorax, 32,[287][288][289][290][291][292][293][294][295] Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery. Exposure to acute hypoxia (barometric pressure 263 mmHg) for 8 hours did not lead to increased numbers of mast cells in the lungs of rats. In contrast, in adult rats kept for 35 days at a barometric pressure of 380 mmHg there was a proliferation of mast cells around the pulmonary blood vessels and in the alveolar septa. This hyperplasia of lung mast cells in response to chronic hypoxia was reversible on removal of the hypoxic stimulus. There was a correlation between the logarithm of the perivascular lung mast cell density (defined in the paper) and the logarithm of the right ventricular weight. There was no increase in the mast cells in the carotid bodies of the hypoxic rats. Young male, old male, young female, and old female rats which had been subjected for 39 days to a barometric pressure of 380 mmHg showed a proliferation of mast cells around the pulmonary blood vessels and in the alveolar walls. This response was greatest in the adult animals and independent of their sex. In the age and sex experiment there was a correlation between the perivascular lung mast cell density and the medial thickness of the muscular pulmonary arteries. Since mast cell hyperplasia has been reported as preceding right ventricular hypertrophy, it is conceivable that mast cell proliferation in the lung may be a defence mechanism to limit the severity of hypoxic pulmonary hypertension rather than to mediate it.During the past few years we have carried out a series of experiments on the effects of chronic alveolar hypoxia on the lungs and heart. Among other things we have investigated the reversibility of the morbid anatomical changes induced in the heart and small pulmonary arteries (Abraham et al., 1971), and pulmonary trunk and carotid bodies (Heath et al., 1973), and the effects of age and sex on the response of the right ventricle and pulmonary vasculature to hypoxia (Smith et al., 1974).Recently the role of the mast cells in the hypoxic lung has aroused interest, and it has been suggested that in rats and guinea-pigs the perivascular pulmonary mast cell may be an important structure in the mediation of the pulmonary vasoconstrictor response to acute alveolar hypoxia (Haas and Bergofsky, 1972). Exposure of rats to chronic hypoxia for three weeks has been reported as leading to a proliferation of mast cells around small pulmonary blood vessels and within the alveolar walls (Kay et al., 1974;Mungall and Barer, 1975;Mungall, 1976). The magnitude of the mast cell hyperplasia correlates with the degree of right ventricular hypertrophy, suggesting that in the rat pulmonary mast cells may be connected in some way with chronic hypoxic pulmonary hypertension.To investigate this problem further, we have exposed rats to severe acute hypoxia to see if hyperplasia of mast cells occurs in their lungs. We have also carried out a retrospective study on lung tissue derived from two previous chron...

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

See 1 more Smart Citation

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

Williams¹,

Heath²,

Kày³

et al. 1977

Thorax

View full text Add to dashboard Cite

show abstract

“…Although BW 48/80, which reputedly releases histamine from mast cells, abolished the hypoxic response in cats [Barer and McCurrie, 1969;Hauge and Staub, 1969;Dawson, Delano, Hamilton and Stekiel, 1974], there is evidence that this action is nonspecific [Barer and McCurrie, 1969;Dawson et al, 1974]. However, there seems to be some link between mast cells and hypoxia because mast cell hyperplasia is found in the lungs of chronically hypoxic rats [Kay, Waymire and Grover, 1974;Mungall, 1976;Mungall and Barer, 1976]. It is disputed as to whether histamine is released from mast cells during hypoxia [Haas and Bergofsky, 1972;Mungall, 1976;Kay et al, 1974].…”

Section: Ratsmentioning

confidence: 99%

H₁ AND H₂ HISTAMINE ACTIONS ON LUNG VESSELS; THEIR RELEVANCE TO HYPOXIC VASOCONSTRICTION

Barer¹,

Emery²,

Mohammed³

et al. 1978

Exp Physiol

View full text Add to dashboard Cite

Pulmonary vasomotor actions of histamine and the possible relationship of histamine to hypoxic pulmonary vasconstriction were studied in anaesthetized cats with one lobe of lung perfused at constant flow and in isolated perfused rat and ferret lungs. In the cat histamine caused dilatation, biphasic responses and constriction with increasing doses. Histamine induced dilatation was better demonstrated during hypoxic vasoconstriction and was reduced by an H2 histamine antagonist; constriction with histamine was abolished by an H1 antagonist. kistamine also caused both vasodilatation and vasoconstriction in ferret lungs. A mast cell stabilizing agent had no effect on hypoxic pulmonary vasoconstriction in cats or rats. This response was unaffected in cats but greatly reduced in rats and ferrets by cyproheptadine, a combined histamine and 5-hydroxytryptamine inhibitor. It was unaffected in cats but abolished in ferrets by an H1 histamine inhibitor. It was again unaffected in cats but greatly reduced in rats and ferrets bv an H2 histamine inhibitor. These species differences may reflect differences in mechanism but more probably reflect nonspecific effects of the inhibitors in certain circumstances. However, when drugs nearly abolished hypoxic vasoconstriction, ATP still caused vasoconstriction.Histamine constricts pulmonary vascular and alveolar duct smooth muscle. It may be released from mast cells and discharged into pulmonary veins during hypoxia [Haas and Bergofsky, 1972]. In rats the pulmonary vasoconstriction caused by hypoxia was modified by drugs inhibiting, releasing or enhancing histamine [Hauge, 1968]. It has therefore been proposed that histamine might be a transmitter responsible for hypoxic vasoconstriction. The hypothesis cannot be sustained in its original form. Histamine has been shown to cause pulmonary vasodilatation as well as vasoconstriction [Dawes and Mott, 1962;Barer, 1966;Shaw, 1971;Silove and Simcha, 1973;Howard, Barer, Thompson, Warren, Abbott and Mungall, 1975;Thompson, Barer and Shaw, 1976], and the drugs affecting hypoxic vasoconstriction in the rat are ineffective in other species [Barer and McCurrie, 1969;Howard et al, 1975;Tucker, Weir, Reeves and Grover, 1976].Our objective was first to clarify the two actions of histamine in terms of dose-response relationships and by the use of antagonistic drugs to see whether they are attributable to the two types of histamine receptor [Ash and Schild, 1966]. Second, we tried to clarify the relation ofhistamine to hypoxic pulmonary vasoconstriction. We used three species. We compared the cat in which H1 histamine receptor antagonists have not abolished hypoxic vasoconstriction

show abstract

“…We conclude that CS interferes with the mechanism(s) responsible for hypoxic pulmonary vasoconstriction in newborn lambs. (Pediatr Res 23: 513-518,1988) HPV, hypoxic pulmonary vasoconstriction CS, cromolyn sodium Other studies have refuted the importance of mast cells in the pulmonary pressor response to hypoxia in cats (5), mast celldeficient mice (6), and rats (7). Despite these interspecies differences, a contributing role for mast cells in HPV remains an attractive hypothesis because of the strategic perivascular location of these calls in the lung (3,4,8), and the variety of vasoactive mediators contained within them (9).…”

mentioning

confidence: 99%

Pulmonary Vascular Response to Aerosolized Cromolyn Sodium and Repeated Epochs of Isocapneic Alveolar Hypoxia in Lambs

1988

View full text Add to dashboard Cite

ABSTRACX. We investigated the effect of aerosolized cromolyn sodium (CS) on the pulmonary vascular response to isocapneic alveolar hypoxia in chronically instrumented lambs aged 11-12 days. Each lamb underwent two operations: chest instrumentation for measurements of pulmonary arterial, systemic arterial, and left atrial pressures, and pulmonary blood flow; and a tracheotomy for drug administration. The animals were recovered 3 days before study. Each lamb received an aerosol of normal saline (placebo) and CS in paired experiments 24 h apart. In the first set of experiments (n = 8), placebo or CS (30 mg) was given, followed by four 15-min epochs of alveolar hypoxia (8% 02, 5% COs 87% N3 each separated by 30 min of alveolar normoxia (21% 02). During hypoxia after both placebo and CS, pulmonary arterial pressure and resistance increased. This response was unchanged with repeated epochs. In the second set of experiments (n = 8), normal saline or CS (30 mg) was administered three times over a 90-min period, followed by one 15-min epoch of hypoxia. Pulmonary arterial pressure and resistance increased during hypoxia after placebo, but did not change after CS. Thus, the single dose of aerosolized CS did not alter the pulmonary vascular response to alveolar hypoxia, whereas the triple dose of CS attenuated the response. Additionally, the pulmonary vascular response to hypoxia alone was not altered by repeated exposures to hypoxia. We conclude that CS interferes with the mechanism(s) responsible for hypoxic pulmonary vasoconstriction in newborn lambs. (Pediatr Res 23: 513-518,1988) HPV, hypoxic pulmonary vasoconstriction CS, cromolyn sodium Other studies have refuted the importance of mast cells in the pulmonary pressor response to hypoxia in cats (5), mast celldeficient mice (6), and rats (7). Despite these interspecies differences, a contributing role for mast cells in HPV remains an attractive hypothesis because of the strategic perivascular location of these calls in the lung (3,4,8), and the variety of vasoactive mediators contained within them (9).CS is a known inhibitor of mast cell degranulation and when administered intravenously, has been shown to inhibit or modify HPV in adult sheep (4), dogs (10, 1 I), and newborn lambs (12). Administration of CS by aerosolization directly into the airways would provide an alternative route of delivery and might offer a more efficient means of locally depositing the drug. Partial blockade of HPV has been demonstrated in adult sheep after treatment with aerosolized CS (13). The purpose herein was to investigate the effect of aerosolized CS on the pulmonary vascular response to repeated epochs of isocapneic alveolar hypoxia in newborn lambs. METHODSSixteen lambs (4.6 + 1.3 kg), 1 1-12 days of age, were used for these experiments. Each lamb was separated from its ewe at 3 days of age in preparation for surgery and housed in a plexiglass cage (3 x 4 ft) with continuous access to an artificial lamb's milk diet (Lamb Milk Replacer, Land O'Lakes, Inc., Fort Dodge, IA). The animal...

show abstract

Hypoxia and lung mast cells: influence of disodium cromoglycate.

Cited by 29 publications

References 28 publications

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

H₁ AND H₂ HISTAMINE ACTIONS ON LUNG VESSELS; THEIR RELEVANCE TO HYPOXIC VASOCONSTRICTION

Pulmonary Vascular Response to Aerosolized Cromolyn Sodium and Repeated Epochs of Isocapneic Alveolar Hypoxia in Lambs

Contact Info

Product

Resources

About

Hypoxia and lung mast cells: influence of disodium cromoglycate.

Cited by 29 publications

References 28 publications

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

Lung mast cells in rats exposed to acute hypoxia, and chronic hypoxia with recovery.

H1 AND H2 HISTAMINE ACTIONS ON LUNG VESSELS; THEIR RELEVANCE TO HYPOXIC VASOCONSTRICTION

Pulmonary Vascular Response to Aerosolized Cromolyn Sodium and Repeated Epochs of Isocapneic Alveolar Hypoxia in Lambs

Contact Info

Product

Resources

About

H₁ AND H₂ HISTAMINE ACTIONS ON LUNG VESSELS; THEIR RELEVANCE TO HYPOXIC VASOCONSTRICTION