Alteration of monocrotaline pyrrole‐induced cardiopulmonary effects in rats by hydralazine, dexamethasone or sulphinpyrazone

Abstract

1The effects of intraperitoneal hydrallazine, dexamethasone, or sulphinpyrazone on the toxicity of monocrotaline pyrrole (MCTP) were examined in rats 14 days after injection of MCTP (5 mgkg-', i.v.).2 MCTP alone caused increases in lung weight, and of both lactate dehydrogenase activity and protein concentration in bronchopulmonary lavage fluid. Right ventricular hypertrophy also occurred.3 Hydrallazine (3mg kg-1, daily), a vasodilator and platelet prostaglandin synthesis inhibitor, reduced the degree of right ventricular hypertrophy and the elevation in the concentration of protein in lavage fluid. 4 Dexamethasone (27 tg kg-, daily), an anti-inflammatory agent and inhibitor of phospholipase, also reduced the right ventricular hypertrophy and the increased protein concentration in lavage fluid caused by MCTP. 5 Sulphinpyrazone (100mg kg-, twice daily), an inhibitor of platelet prostaglandin biosynthesis, prevented right ventricular hypertrophy in the MCTP treated rats without affecting any of the indices of lung injury. 6 These results provide further support for the hypothesis that platelets and vasoconstrictor agents play a role in the development of MCTP-induced pulmonary hypertension.

Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats

“…5) PASMCs isolated from pulmonary hypertensive rats appeared relatively resistant to the BMPR2 mRNA increase and the antiproliferative effects of dexamethasone. Effect of dexamethasone treatment (day 14-28) on the degree of muscularisation of peripheral pulmonary arteries: a total of 30 intra-acinar vessels were analysed in each of three lung sections from each rat exposed to monocrotaline (MCT) for 28 days and dexamethasone-treated groups (days [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Monocrotaline is an ''inflammatory'' model of PAH, comprising an initial asymptomatic inflammatory phase, followed by a less inflammatory symptomatic phase from day 14, with increased medial volume in both major and intra-acinar pulmonary arteries by 21 days exposure [38,39]. Previous studies have similarly shown that preventive immunosuppressive therapy is effective in MCT-induced PAH when given before the onset of pulmonary vascular remodelling (i.e.…”

“…[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] dexamethasone-treated group (MCT+Dex D21-35) (n510 per group). All rats had access to standard rat chow and water ad libitum.…”

“…Immunosuppressive therapies including rapamycin [17] and cyclosporin [18] have been shown to attenuate the development of PAH in rats exposed to MCT, including established PAH [17,18]. Earlier studies have shown that steroids prevent the development of MCT-induced PAH [9,[19][20][21], although no studies have yet shown that steroids reverse established MCT-induced PAH.…”

Role of serotonin in the pathogenesis of acute and chronic pulmonary hypertension

“…94 Plasma serotonin levels are increased, coinciding with platelet accumulation in the lungs, the vasoconstrictor response to serotonin is enhanced, and both pulmonary artery pressure and the severity of histological changes are reduced by selective serotonin blockade and by inhibition of serotonin synthesis with chlorophenylalanine 5395 96 The hypertensive effect of monocrotaline was reduced in rats made moderately thrombocytopenic with antiplatelet serum,97 and by the platelet modifying drug sulphinpyrazone 98. Prednisolone was also beneficial 99.…”

Cardiac and Vascular Atrogin-1 mRNA Expression is Not Associated with Dexamethasone Efficacy in the Monocrotaline Model of Pulmonary Hypertension

“…The more substantial dexamethasone-induced improvement in RV/LVS reported by Hilliker and Roth [30] may relate to differences in the treatment regimen, which in their seminal study began 3 days prior to injection of the MCT pyrrole, whereas in the present study it was initiated 28 days after MCT injection. We had hypothesized that the well-documented effect of dexamethasone on myostatin would lead to atrophic changes in both the vascular and cardiac tissues.…”