Selective Attenuation of Enhanced Angiotensin Ii Mediated Responses in the Streptozotocin Diabetic Rat Thoracic Aorta By Tempol

摘要

Summary. Previous studies suggest the role of superoxide anion radicals (O2"~) as endothe-lium derived contractile /actor. However, their role in the enhanced responses to angiotensin II (Ang II) or phenylepbrine (PE) and diminished relaxation responses to acetylcholine (ACh) in diabetes remain unclear. In the present study, we investigated the possible involvement of O2~ in the Ang II-, PE- and ACh-mediated responses. Aortic rings were obtained from strep-tozotocin (STZ)-diabetic rats and contractile responses to Ang II and PE, and relaxation responses to acetylcholine (ACh) were assessed in presence of tempol. The contractile responses to Ang II and PE were significantly increased and the ACh mediated responses were impaired. Ang II and PE mediated responses in control rat aorta were unaffected by the presence of tempol (100JJM). The increase in responses to Ang II in diabetic aorta was decreased in presence of tempol (100J0.M) but the PE mediated responses remained unchanged. Further, the impaired ACh mediated relaxation in diabetic aorta were restored by tempol. Removal of the endothelium led to an increase in the maximal response to Ang II and PE in both control and diabetic aorta. Tempol did not alter the responses to Ang II in endothelium-denuded aorta. The present findings indicate that O2~ may be involved in the increased contractile responses to Ang II but not PE in the diabetic rat thoracic aorta and this is endothelium dependent.