PT340 Age-related impairment in androgen stimulation of vascular endothelial growth factor-mediated angiogenesis

Abstract

Introduction: Ang 1-7 appeares as an intrigant peptide regulating AT1 receptor activity and effects. Objectives: The in vitro evaluation of rat aorta and coronary system response on action of the different neuroendocrine factors, inclusively Ang 1-7, in diabetes induced endothelial dysfunction. Methods: Diabetes induced endothelial dysfunction (DED) was reproduced by streptozotocin administration in rats. Using the models of isolated aorta ring and isovolumic heart perfusion the vascular response (relaxant or constricting) and coronary flux were determined on action of acetylcholine (Ach), bradykinin, Ang 1-7, Ang II (inclusively in condition of mas receptor blockade by A779), hydrogen peroxide, norepinephrine and endothelin-1. Results: The Ach action up on phenylephrine induced aorta ring contraction manifested in DED by significant vasorelaxation reduction by up to 36% vs control pattern. Remarkably, Ang 1-7 (10-10 M) has induced an aortic ring relaxation similarly to control level, achieving a range of 11,4-26,5%. The Ang II induced constrictor plateau is significantly elevated in DED by 51,9%. However, it decreases by 32,8% when a premedication by Ang 1-7 is performed, and, contrarily, raises by 36,4% when mas receptors are blocked by A779. Norepinephrine and endothelin-1 have induced in DED an aorta contraction increasing by 34-42%. The analogous events were fixed in heart. Thus, functional coronary reserve is reduced in DED on Ach and bradykinin action by 38 and 31%, respectively. Nevertheless, coronary reserve is not affected during Ang 1-7 action compared to control index: 8,84 vs 9,86% (p>0,05). Coronary flux on Ang II action is decreased more pronounced by 46%, but the decline is limited by almost 50% in condition of Ang 1-7 administration. The mas receptor blocking led to Ang II induced coronary flow diminution more by 52%. Interestingly, the hyperpolarization induced coronary dilation level related to hydrogen peroxide action is not impaired in DED. Conclusion: 1. Vasorelaxation and coronary dilation effects of Ang 1-7 are not impaired in diabetes induced endothelial dysfunction, event that may be emphasized as compensator pattern considering the fact of affected cholinergic vascular response. 2. Ang 1-7 significantly reduces Ang II induced vasoand coronary constricting effects, but mas receptor blocking, contrarily, leads to their augmentation. Disclosure of Interest: None Declared