Endothelin-1 and thromboxane A2 increase pulmonary vascular resistance in granulocyte-mediated lung injury

Abstract

Activated granulocytes seem to enhance pulmonary vascular resistance via endothelin-1 and thromboxane A2. The endothelin-1 effects are probably mediated via endothelin-A receptors since the endothelin-A receptor antagonist LU135252 was able to suppress the early pressure reaction after FMLP injection, whereas the cyclooxygenase inhibitor diclofenac was able to reduce the second pressure increase.

Inhaled levosimendan reduces mortality and release of proinflammatory mediators in a rat model of experimental ventilator-induced lung injury*

“…Previous studies demonstrated that induction of local, proinflammatory mediators in the lung plays a pivotal role in the development and severity of VILI (5-7). Those mediators and alterations within the lung architecture lead to the hemodynamic alterations induced by pulmonary hypoxic vasoconstriction and increased right heart pressures (2,9,10).…”

“…Previous studies demonstrated that excessive inflation with high tidal volumes can induce lung inflammation via activation of neutrophils and release of inflammatory cytokines (5-7). Therefore, local and systemic activation of proinflammatory mediators during VILI plays a pivotal role in inducing local and systemic organ failure (5).Mechanical disruption of the alveolarepithelial membrane causes pulmonary edema with subsequent excessive pulmonary vasoconstriction related to developing hypoxemia (8,9). These alterations in the lung may result in pulmonary hypertension followed by right heart failure and death (10).…”

“…Mechanical disruption of the alveolarepithelial membrane causes pulmonary edema with subsequent excessive pulmonary vasoconstriction related to developing hypoxemia (8,9). These alterations in the lung may result in pulmonary hypertension followed by right heart failure and death (10).…”

Pretreatment with perfluorohexane vapor attenuates fMLP-induced lung injury in isolated perfused rabbit lungs

“…This corresponds to the increase in filtration coefficient and bronchoalveolar lavage protein concentration that has been reported to occur not earlier than 60 minutes after fMLP in isolated perfused rabbit lungs [19]. The observed increase in 6-keto-PGF 1α after fMLP challenge in the control, which has been described during the induction of acute lung injury [20], seems to have had no protective effects on the pulmonary vasculature. This is most likely due to the change in balance between TXB 2 and 6-keto-PGF 1α liberation.…”

“…As described in detail before [20] {2593 /id}, Chinchilla rabbits (n = 34; 2.9 ± 0.5 kg) were anesthetized with ketamine, 50 mg/kg ( …”