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Effect of Photodynamic Therapy on the Endothelium-dependent Relaxation of Isolated Rat Aortas¹

Department of Biochemistry, Cardiovascular Research Institute, Erasmus University Rotterdam (COEUR) [M. J. G., L. E. A. van de M., J. F. K., W. S.], and Dr. Daniel Den Hoed Cancer Center [W. M. S.], Rotterdam, the Netherlands

The early vascular effects of photodynamic therapy (PDT) include transient vasoconstriction and platelet aggregation. Since endothelium-derived relaxing factor (EDRF) is a potent vasodilator and inhibitor of platelet aggregation, we questioned whether PDT impairs the production of EDRF.

To study this possible effect of PDT, endothelium-dependent relaxations of thoracic aortas obtained from male Wistar rats were determined. The aortic rings were connected to a isometric force transducer, exposed to various doses of Photofrin porfimer sodium (Photofrin) (0.1–1.0 µg/ml), and illuminated with red light (wavelength > 610 nm, 14.6 ± 1.5 mW/cm²) for different time periods (5–25 min). Endothelium-dependent relaxation was induced by acetylcholine in precontracted aortic rings. This EDRF-mediated relaxation was decreased after PDT in a light dose- and drug dose-dependent manner. Light microscopic examination did not show loss of endothelial cells. Similar results were obtained with rat aortas exposed to Photofrin in vivo and illuminated in vitro. Direct smooth muscle relaxation induced with sodium nitroprusside was not impaired, showing that PDT did not reduce the ability of smooth muscles to relax. No effect on the contractile responses was found either.

We conclude that PDT impairs the production or release of EDRF by the endothelium. This could play an important role in the initial events occurring in vivo during and after PDT.

¹ Supported by Dutch Cancer Society Grant EUR 91-01 and a donation from Mrs. E. C. Bakker-Grieszmayer.

² To whom requests for reprints should be addressed, at the Department of Biochemistry, Cardiovascular Research Institute, Erasmus University Rotterdam, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands.

Received 11/17/92. Accepted 3/29/93.