P110	Gamma-irradiation induces senzitization of endothelium-dependent and endothelium-independent relaxation of rat aorta.
1C.J.Beller, 1L.Seres, 1T.Radovits, 1J.Kosse, 2R.Krempien, 1S.Hagl, 1G.Szabó
1Department of Cardiac Surgery, University of Heidelberg, Heidelberg, DE; 2Department of Clinical Radiology, University of Heidelberg, Heidelberg, DE.

Objective: Post-irradiation endothelial dysfunction and/or alterations of smooth muscle cells may lead to altered vascular tone and activation, adhesion and aggregation of platelets. However, there are confounding data about the vasomotor effects of radiotherapy. Therefore this study focused on acute and prolonged effects of irradiation (1 day and 7 days post irradiation) on the isometric tension and the vasorelaxation of isolated rat thoracic aorta. Methods: For acute experiments the excised aortic rings were exposed to external gamma-irradiation with 20 Gy. Aortae of in vivo-irradiated rats (20 Gy) were harvested after 1 day and 7 days. The aortic rings were placed in isolated organ bath, superfused by oxygenated Krebs-Henseleit buffer and precontracted by phenylephrine (PE). The dose-dependent relaxation to acetylcholine (Ach) and sodium-nitroprusside (SNP) were compared with control rings. Results: The vasoconstrictive response to PE was significantly lower both, acutely and prolonged after irradiation. Furthermore, at day 1 and day 7 post-irradiation the maximal force generated in response to KCl was significantly less for than control rings. Acutely after irradiation, vasorelaxation to Ach and SNP was not different from control rings. Interestingly, vasorelaxation to Ach (1 E-8 M, p<0.05) and SNP (0,5 E-9 M, p<0.05) was significantly enhanced 1 day and 7 days after irradiation . Conclusions: Irradiation alters the vasoconstrictive response to PE of rat aortic rings acutely and prolonged after gamma-irradiation. Vasorelaxation was not altered acutely after irradiation. However, both endothelium-dependent and endothelium-independent relaxation were enhanced 1 day and even 7 days after irradiation. It has to be determined, if this sensitization to relaxing agents may be a compensatory mechanism to increased vascular tone after irradiation or if it may reflect irradiation-induced vasodysregulation.

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