EFECTO DE LA ANGIOTENSINA II EN LA RESPUESTA VASCULAR DE LA AORTA TORÁCICA DEL MODELO DE RATÓN NULO PARA EL GEN DELTA- SARCOGLICANO (δ-SG) CON MIOCARDIOPATÍA DILATADA

Abstract

Introduction: Mutations in the delta sarcoglycan gene (δ-SG ) cause muscular waist dystrophy with cardiomyopathy. For the mouse model deficient in this gene are observed alterations in cardiac muscle and smooth muscle, and also described featuring multiple coronary artery vasoconstriction. However the pathophysiological changes of these vascular changes have not been clarified, so that multiple systems may be involved, such as the renin-angiotensin system, something we consider important. So the aim of this study was to evaluate the effect of angiotensin II in the vascular response of the aorta of a mouse experimental model delta sarcoglycan gene null (δ-SG). Methods: In this protocol we use female mice Knock-out (KO) and wild type (WT) from 5 months old, it were anesthetized with pentobarbital (50 mg/kg IP) and heparine (50 UI), after that we proceeded to dissect the aorta. The aorta was placed in an isolated organ system, which keeps Krebs solution and bubbled with carbogen (95% O2 and 5% CO2). Finally we proceeded to make curves concentration response to angiotensin II (10-9- 10-6 Results: We found a significant difference in contractile vascular response to angiotensin II, it was increased in the knockout mouse. Moreover, we analyze ). 13 whether changes in the vascular response to angiotensin II were due to a decrease in the relaxant response which could result in an increase in the response to angiotensin II in the thoracic aorta, but the data suggests that endothelial ON is not participating significantly in the regulation of the contractile response in these mice. Finally, we determined whether the participation of contractile prostanoids was modified in this disease, for which concentration response curves were performed to angiotensin II in the presence and absence of indomethacin, in an interesting finding that the knockout mice the response was inhibited almost completely unlike normal mouse, suggesting a greater participation of contractile prostanoids in mouse mutant. Followed up with a way to assess whether histological changes in the vascular response is related to structural changes, finding that there is vascular smooth muscle hypertrophy and damage to the endothelial cell layer in both thoracic aorta and coronary artery mutant mouse . Conclusion: There is an increase in contractile vascular response to angiotensin II in KO mouse, these changes do not appear to be significantly involved in the NO in the regulation of vascular contractile response in KO mice. Regarding the participation of contractile prostanoids in this disease, we found a participation of contractile prostanoids in mouse KO. Structural changes were observed in smooth muscle and endothelial KO mouse. Key words: Mouse knock-out, delta sarcoglycan, angiotensin II, cardiomyopathy