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

Abstract

Background: Pulmonary vascular remodeling induced by chronic hypoxia regresses after return to normoxia. This regression is associated with an increased amount of collagenase in pulmonary mast cells and increased collagenolytic and elastolytic activity in the lung tissue. Objective: The role of lung mast cells during recovery from chronic hypoxia was tested by the inhibition of their degranulation by disodium cromoglycate (DSCG). Methods: Male Wistar rats (n = 46) were exposed to isobaric hypoxia (3 weeks, F_iO₂ 0.1). Thirteen of them were tested immediately at the end of exposure, 17 were treated with DSCG during the first 4 days of recovery and tested on the 5th or 14th day of recovery, 16 untreated animals were measured at the same time intervals. These groups were compared with 12 animals kept in normoxia. The rats were anesthetized (Thiopental) and their pulmonary arterial blood pressure (PAP), cardiac output and heart weight were tested, as well as the collagen composition of the walls of the peripheral pulmonary arteries. Results: DSCG applied during the first 4 days of recovery from chronic hypoxia blocked the decrease in PAP during the early phase of recovery and had no influence on PAP at a later phase. DSCG administration prevents collagen splitting in peripheral pulmonary vessels at the early phase of recovery. PAP and right ventricle hypertrophy were normalized after 14 days of return to normoxia. Conclusions: Mast cell degranulation plays a role in the regression of pulmonary hypertension during the early phase of recovery from chronic hypoxia.

Mast cells: an expanding pathophysiological role from allergy to other disorders

“…Therefore, it may be deduced that an inhibition of mast cell degranulation impairs the development but does not affect the established pulmonary hypertension in rats. On the contrary, it has been shown that prevention of mast cell degranulation by disodium cromoglycate delays the regression of hypoxic pulmonary hypertension following chronic hypoxia in rats, suggesting that mast cell degranulation plays a role in the regression of pulmonary hypertension during the early phase of recovery from chronic hypoxia (Maxová et al 2010).…”

Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats

“…Moreover, MCs/c-kit expressing cells have been localized along the periphery/adventitial layer of remodelled pulmonary vessels in experimental PH [19-21]. Recently, MC degranulation has been implicated both in the development of pulmonary vascular remodeling in chronic hypoxic rats and in the regression of the remodeling upon bringing them back to normoxia [22,23]. Activated MCs produce several mediators including the biogenic amine serotonin, the cytokines interleukin (IL)-6 and IL-13, and the serine proteases chymase and tryptase that are capable of activating matrix metalloproteases (MMPs) [9].…”

Recovery from Hypoxic Pulmonary Hypertension in Rats

“…Our previous measurements of cardiac output in normoxic rats, rats exposed to three weeks of hypoxia and rats after 5 and 14 days of recovery in air, did not show any differences (11). If some volume overload occurs at the beginning of hypoxia it lasts for only first few days of acclimatization (14).…”