EFFECT OF PHOTODYNAMIC THERAPY ON THE ENDOTHELIUM-DEPENDENT RELAXATION OF ISOLATED RAT AORTAS

The early vascular effects of photodynamic therapy (PDT) include trans ient vasoconstriction and platelet aggregation. Since endothelium-deri ved relaxing factor (EDRF) is a potent vasodilator and inhibitor of pl atelet aggregation, we questioned whether PDT impairs the production o f EDRF. To study this possible effect of PDT, endothelium-dependent re laxations of thoracic aortas obtained from male Wistar rats were deter mined. The aortic rings were connected to a isometric force transducer , exposed to various doses of Photofrin porfimer sodium (Photofrin) (0 .1-1.0 mug/ml), and illuminated with red light (wavelength > 610 nm, 1 4.6 +/- 1.5 mW/cm2) for different time periods (5-25 min). Endothelium -dependent relaxation was induced by acetylcholine in precontracted ao rtic rings. This EDRF-mediated relaxation was decreased after PDT in a light dose- and drug dose-dependent manner. Light microscopic examina tion did not show loss of endothelial cells. Similar results were obta ined with rat aortas exposed to Photofrin in vivo and illuminated in v itro. Direct smooth muscle relaxation induced with sodium nitroprussid e was not impaired. showing that PDT did not reduce the ability of smo oth muscles to relax. No effect on the contractile responses was found either. We conclude that PDT impairs the production or release of EDR F by the endothelium. This could play an important role in the initial events occurring in vivo during and after PDT.