The Angiotensin-converting enzyme inhibitor captopril inhibits poly(adp-ribose) polymerase activation and exerts beneficial effects in an ovine model of burn and smoke injury.

Abstract

We investigated the effect of the angiotensin-converting enzyme (ACE) inhibitor captopril in a clinically relevant ovine model of smoke and burn injury, with special reference to oxidative stress and activation of poly(ADP-ribose) polymerase, in the lung and in circulating leukocytes. Female, adult sheep (28-40 kg) were divided into three groups. After tracheostomy and under deep anesthesia, both vehicle-control-treated (n = 5) and captopril-treated (20 mg/kg per day, i.v., starting 0.5 h before the injury) (n = 5) groups were subjected to 2 × 20%, third-degree burn injury and were insufflated with 48 breaths of cotton smoke. A sham group not receiving burn/smoke was also studied (n = 5). Animals were mechanically ventilated and fluid resuscitated for 24 h in the awake state. Burn and smoke injury resulted in an upregulation of ACE in the lung, evidenced by immunohistochemical determination and Western blotting. Burn and smoke injury resulted in pulmonary dysfunction, as well as systemic hemodynamic alterations. Captopril treatment of burn and smoke animals improved PaO2/FiO2 ratio and pulmonary shunt fraction and reduced the degree of lung edema. There was a marked increase in PAR levels in circulating leukocytes after burn/smoke injury, which was significantly decreased by captopril. The pulmonary level of ACE and the elevated pulmonary levels of transforming growth factor β in response to burn and smoke injury were significantly decreased by captopril treatment. Our results suggest that the ACE inhibitor captopril exerts beneficial effects on the pulmonary function in burn/smoke injury. The effects of the ACE inhibitor may be related to the prevention of reactive oxygen species-induced poly(ADP-ribose)polymerase overactivation. Angiotensin-converting enzyme inhibition may also exert additional beneficial effects by inhibiting the expression of the profibrotic mediator transforming growth factor β.

• Authors: Sven Asmussen, Eva Bartha, Gabor Olah, Elena Sbrana, Sebastian W Rehberg, Yusuke Yamamoto, Perenlei Enkhbaatar, Hal K Hawkins, Hiroshi Ito, Robert A Cox, Lillian D Traber, Daniel L Traber, Csaba Szabo
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 36 Issue 4 Pg. 402-9 (Oct 2011) ISSN: 1540-0514 [Electronic] United States
• PMID: 21701415 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Nitric Oxide
• Captopril
• Poly(ADP-ribose) Polymerases

Topics

• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Animals
• Blotting, Western
• Burns (drug therapy, enzymology, metabolism)
• Captopril (therapeutic use)
• Enzyme Activation (drug effects)
• Female
• Heart (drug effects)
• Immunohistochemistry
• Leukocytes (metabolism)
• Lung (drug effects)
• Nitric Oxide (metabolism)
• Poly(ADP-ribose) Polymerases (metabolism)
• Respiration, Artificial
• Sheep, Domestic