BACKGROUND: Pulmonary hypertension is the major hemodynamic feature of progressive lung injury. We hypothesized that the mechanisms of pulmonary vasorelaxation become progressively impaired in progressive lung injury. The purpose of this study was to examine the following mechanisms of pulmonary vasorelaxation in a rat model of monocrotaline-induced progressive lung injury: endothelial-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), endothelial-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol), and hypoxic pulmonary vasoconstriction. METHODS: Rats were studied 2, 7, and 14 days after monocrotaline injection (100 mg/kg intraperitoneally). Pulmonary vasomotor control mechanisms were studied in isolated pulmonary artery rings. Controls were studied 14 days after saline injection. Statistical analysis was by ANOVA; p < 0.05 was considered significant. RESULTS: A progressive impairment of pulmonary vasorelaxation was observed. By 14 days after monocrotaline injection acetylcholine produced only 25% +/- 5% relaxation versus 95% +/- 5% in controls (p < 0.05), nitroprusside produced 46% +/- 5% relaxation versus 100% in controls (p < 0.05), and isoproterenol produced only 18% +/- 5% relaxation versus 94% +/- 4% in controls (p < 0.05). At the same time hypoxic pulmonary vasoconstriction became progressively exaggerated. CONCLUSIONS: Progressive dysfunction of pulmonary vasomotor control may contribute to the pulmonary hypertension seen in progressive lung injury.
BACKGROUND:Pulmonary hypertension is the major hemodynamic feature of progressive lung injury. We hypothesized that the mechanisms of pulmonary vasorelaxation become progressively impaired in progressive lung injury. The purpose of this study was to examine the following mechanisms of pulmonary vasorelaxation in a rat model of monocrotaline-induced progressive lung injury: endothelial-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), endothelial-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol), and hypoxic pulmonary vasoconstriction. METHODS:Rats were studied 2, 7, and 14 days after monocrotaline injection (100 mg/kg intraperitoneally). Pulmonary vasomotor control mechanisms were studied in isolated pulmonary artery rings. Controls were studied 14 days after saline injection. Statistical analysis was by ANOVA; p < 0.05 was considered significant. RESULTS: A progressive impairment of pulmonary vasorelaxation was observed. By 14 days after monocrotaline injection acetylcholine produced only 25% +/- 5% relaxation versus 95% +/- 5% in controls (p < 0.05), nitroprusside produced 46% +/- 5% relaxation versus 100% in controls (p < 0.05), and isoproterenol produced only 18% +/- 5% relaxation versus 94% +/- 4% in controls (p < 0.05). At the same time hypoxic pulmonary vasoconstriction became progressively exaggerated. CONCLUSIONS: Progressive dysfunction of pulmonary vasomotor control may contribute to the pulmonary hypertension seen in progressive lung injury.
Authors: Helen Christou; Ossama M Reslan; Virak Mam; Alain F Tanbe; Sally H Vitali; Marlin Touma; Elena Arons; S Alex Mitsialis; Stella Kourembanas; Raouf A Khalil Journal: Am J Physiol Lung Cell Mol Physiol Date: 2012-01-27 Impact factor: 5.464
Authors: Helen Christou; Hannes Hudalla; Zoe Michael; Evgenia J Filatava; Jun Li; Minglin Zhu; Jose S Possomato-Vieira; Carlos Dias-Junior; Stella Kourembanas; Raouf A Khalil Journal: J Pharmacol Exp Ther Date: 2017-12-06 Impact factor: 4.030
Authors: Virak Mam; Alain F Tanbe; Sally H Vitali; Elena Arons; Helen A Christou; Raouf A Khalil Journal: J Pharmacol Exp Ther Date: 2009-11-13 Impact factor: 4.030
Authors: David J R Fulton; Xueyi Li; Zsuzsanna Bordan; Stephen Haigh; Austin Bentley; Feng Chen; Scott A Barman Journal: Antioxidants (Basel) Date: 2017-07-06