INVESTIGADORES
ROZENFELD Paula Adriana
congresos y reuniones científicas
Título:
Aortic smooth muscle reactivity in ƒÑ-ƒ{galactosidase A knockout mice.
Autor/es:
ROZENFELD PA; FRITZ M; ASHOK K; BRADY R; FOSSATI CA; RINALDI G
Lugar:
New Orleans, USA
Reunión:
Congreso; : 56th. Annual Meeting of the American Society of Human Genetics; 2006
Resumen:
Introduction: Fabry disease results in deposition of glycosphingolipids, particularly in vascular endothelium and smooth muscle cells, leading to vessel occlusion and ischemia. Previous reports demonstrated increased endothelium-mediated vascular reactivity in Fabry disease. We used the agalactosidase A knockout (AGA null) mice as a murine model to study the pathophysiology of the vasculopathy in Fabry disease. The aim of this work was to evaluate the aortic reactivity in AGA null mice compared with wild type littermates (WT). Methods: Contraction forces (in milligrams of force per milligram of tissue, mgF/mgT) of aortic rings from AGA null and WT mice were measured after exposure to either 80 mM KCl or 1 µM norepinephrine (NE). The relaxant agents acethylcholine (Ach) and sodium nitroprusside (SNP) were added to the bath when the maximum force of the agonists was attained, and the relaxation was expressed as a percent of that contraction. The effect of L-NAME in Ach-induced relaxation was also studied. Results: Aortic rings from AGA null mice developed a higher contractile force than WT mice in 80 mM KCl (1526 ± 169 vs. 1083 ± 117 mgF/mgT, P<0.05); and with NE (1412 ± 119 vs. 1174 ± 141 mgF/mgT,). After the addition of Ach, the relaxation was significantly greater in AGA null mice. L-NAME inhibited Ach-induced relaxation to a similar extent in both groups. The percentage of relaxation with  SNP was lower in AGA null mice than in WT mice (p<0.03). Conclusions: 1) Aortic smooth muscle of AGA null mice exhibited augmented contractile response upon activation of either voltage-operated or receptor-operated channels. 2) An exaggerated response to Ach was observed, demonstrating an increased endothelium-dependent vasodilation. 3) SNP-induced relaxation was significantly decreased in AGA nulls with respect to WT. 4) A similar blunting of Ach response after L-NAME was observed in both groups. These findings indicate an augmented contractile response and a higher vasodilation response in AGA null mice mediated mainly by non-NO endothelial mediators.