Journal of Applied Physiology, Vol 62, Issue 1 47-54, Copyright © 1987 by American Physiological Society

ARTICLES

Pharmacological modification of pulmonary vascular injury: possible role of cAMP

I. S. Farrukh, G. H. Gurtner and J. R. Michael

Experiments were designed to test the hypothesis that drugs which increase adenosine 3',5'-cyclic monophosphate (cAMP) in the lung would prevent the pulmonary hypertension and the increase in vascular permeability caused by the infusion of the oxidant lipid peroxide, tert-butyl hydroperoxide (t-bu-OOH), in isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pretreatment with indomethacin or verapamil was also studied, since these drugs block the increase in pulmonary arterial pressure caused by t-bu-OOH. Indomethacin or verapamil prevented the pulmonary hypertension but did not prevent the increase in permeability caused by t-bu-OOH. Consequently, indomethacin or verapamil treatment partially reduced the gain in lung weight caused by t-bu-OOH. In contrast, pretreatment with isoproterenol, prostaglandin E1, or a cAMP analogue not only prevented the pulmonary hypertension but also inhibited the increase in vascular permeability caused by t-bu-OOH. Consequently, these drugs completely blocked the gain in lung weight caused by t-bu-OOH. Posttreatment with aminophylline or the cAMP analogue also significantly reduced the gain in lung weight caused by t-bu-OOH. These results indicate that pharmacological therapy can reduce the pulmonary hypertension and the increase in vascular permeability caused by the infusion of a lipid hydroperoxide. Since isoproterenol, aminophylline, prostaglandin E1, and a cAMP analogue all had similar effects, the results suggest that the likely common mechanism for their protective effect is an increase in cAMP.

This article has been cited by other articles:

				S. L. Sayner, D. W. Frank, J. King, H. Chen, J. VandeWaa, and T. Stevens Paradoxical cAMP-Induced Lung Endothelial Hyperpermeability Revealed by Pseudomonas aeruginosa ExoY Circ. Res., July 23, 2004; 95(2): 196 - 203. [Abstract] [Full Text] [PDF]

				R. Coimbra, A. Razuk-Filho, M. M. Yada-Langui, and M. Rocha-e-Silva Intraarterial Pulmonary Pentoxifylline Improves Cardiac Performance and Oxygen Utilization After Hemorrhagic Shock: A Novel Resuscitation Strategy Anesth. Analg., May 1, 2004; 98(5): 1439 - 1446. [Abstract] [Full Text] [PDF]

				S. C. HOFFMANN, M. S. BLEIWEIS, D. R. JONES, H. C. PAIK, P. CIRIACO, and T. M. EGAN Maintenance of cAMP in Non-Heart-Beating Donor Lungs Reduces Ischemia-Reperfusion Injury Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1642 - 1647. [Abstract] [Full Text] [PDF]

				M. S. Bleiweis, D. R. Jones, S. C. Hoffmann, R. M. Becker, and T. M. Egan Reduced ischemia-reperfusion injury with rolipram in rat cadaver lung donors: effect of cyclic adenosine monophosphate Ann. Thorac. Surg., January 1, 1999; 67(1): 194 - 199. [Abstract] [Full Text] [PDF]

				X.-W. JIANG, K. KAMBARA, N. GOTOH, K. NISHIGAKI, and H. FUJIWARA Effects of Low-Dose Beraprost Sodium, a Stable Prostaglandin I2 Analogue, on Reperfusion Injury to Rabbit Lungs Am. J. Respir. Crit. Care Med., November 1, 1998; 158(5): 1669 - 1675. [Abstract] [Full Text] [PDF]

				T. M. Moore, P. M. Chetham, J. J. Kelly, and T. Stevens Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP Am J Physiol Lung Cell Mol Physiol, August 1, 1998; 275(2): L203 - L222. [Abstract] [Full Text] [PDF]

				P. V. Petrik, B. Braithwaite, W. S. Moore, H. A. Gelabert, and W. Quinones-Baldrich Pentoxifylline Improves Skeletal Muscle Recovery After Acute Ischemic and Reperfusion Injury Vascular and Endovascular Surgery, January 1, 1998; 32(1): 5 - 12. [Abstract] [PDF]

				T. Nakamura, T. Hirata, T. Fukuse, M. Ueda, S. Hitomi, and H. Wada DIBUTYRYL CYCLIC ADENOSINE MONOPHOSPHATE ATTENUATES LUNG INJURY CAUSED BY COLD PRESERVATION AND ISCHEMIA-REPERFUSION J. Thorac. Cardiovasc. Surg., October 1, 1997; 114(4): 635 - 642. [Abstract] [Full Text]

				H. Wada, C. J. Liu, T. Hirata, T. Bando, and S. Kosaka Effective 30-Hour Preservation of Canine Lungs With Modified ET-Kyoto Solution Ann. Thorac. Surg., April 1, 1996; 61(4): 1099 - 1105. [Abstract] [Full Text]