Effects of radiation therapy on vascular responsiveness

The use of radiation therapy to inhibit vascular proliferative diseases has produced encouraging results in several clinical trials. However, little i s known about the possible side effects of radiation on vascular responsive ness. Our goal was to study the in vitro vascular responses of the rabbit a orta to various agonists immediately after several regimens of radiation th erapy administered at doses prescribed in clinical protocols and at two dif ferent dose rates, High-dose-rate radiation was administered either by brac hytherapy, using a gamma source, iridium 192, or an external electron beam producing beta radiation. Low-dose-rate radiation was administered by brach ytherapy using a liquid-filled balloon with the beta emitter P-32. Vascular reactivity after the various regimens of irradiation was determined using the organ bath pharmacology assay. Various agonists were applied to the rab bit aorta to produce full cumulative concentration-response curves. Radiati on, administered using an external electron beam, did not alter endothelium -dependent relaxation of the aorta induced by acetylcholine. However, the u se of a catheter-based system to deliver radiation disrupted the endothelia l cell lining of the vessel, causing a lack of relaxation by acetylcholine. Therefore, to compare all modalities of radiation therapy on vascular resp onsiveness, the agonists used in this study are known to act directly on th e smooth muscle. Radiation therapy had no effect on the contractile respons es induced by the following agonists: phenylephrine and potassium chloride. Vascular dilatation induced by nitroglycerin, a nitric oxide donor, was un affected by radiation therapy. The contractile response induced by des-Arg( 9)-bradykinin, a kinin B-1 receptor agonist, was significantly increased tw ofold to threefold by all types of irradiation under study. This enhanced r esponse is attributable to an increase of mRNA levels coding for this recep tor. In all cases, radiation therapy did not alter the effective concentrat ion producing 50% of maximal responsiveness (EC,,) and did not reduce the v ascular responsiveness induced by agonists, Taken together, we conclude tha t radiation therapy does not hinder endothelium-independent vascular respon siveness and increases the kinin B-1 receptor-mediated vasoconstriction.