Martinelli, A.M.; de Moraes, L.H.O.; de Moraes, T.F.; Rodrigues, G.J. Guanylyl Cyclase Activator Improves Endothelial Function by Decreasing Superoxide Anion Concentration. J. Vasc. Dis.2024, 3, 102-111.
Martinelli, A.M.; de Moraes, L.H.O.; de Moraes, T.F.; Rodrigues, G.J. Guanylyl Cyclase Activator Improves Endothelial Function by Decreasing Superoxide Anion Concentration. J. Vasc. Dis. 2024, 3, 102-111.
Martinelli, A.M.; de Moraes, L.H.O.; de Moraes, T.F.; Rodrigues, G.J. Guanylyl Cyclase Activator Improves Endothelial Function by Decreasing Superoxide Anion Concentration. J. Vasc. Dis.2024, 3, 102-111.
Martinelli, A.M.; de Moraes, L.H.O.; de Moraes, T.F.; Rodrigues, G.J. Guanylyl Cyclase Activator Improves Endothelial Function by Decreasing Superoxide Anion Concentration. J. Vasc. Dis. 2024, 3, 102-111.
Abstract
Introduction: activation of soluble guanylyl cyclase (sGC) in smooth muscle vascular is able to induces vasodilation. The chronic activation of sGC was able to improves vascular function in congestive heart failure animal model. Thus, activation of sGC can be a way to vasodilation and improvement in endothelial function. Objective: Investigate whether the selective activator of sGC can revert the endothelial dysfunction, and investigate the mechanism of action. Methods: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact aortic rings were placed in a myograph and incubated with atacicguat 0.1 µM during 30 min. Cumulative concentration-effect curves to acetylcholine (Ach) were performed to measure the endothelial function. The pD2 and maximum relaxant effect (Emax) was measured to Ach. In endothelial cell culture, the detection of superoxide anion (O2•-) was made by using fluorescent probes, including DHE and lucigenin. Results: Ataciguat improved the relaxation induced by acetylcholine in 2K-1C(pD2: 6.99 ±0.08, n=6) compared to control(pD2: 6.43±0.07, n=6, p<0.05), also improved in aortic rings from 2K(pD2: 7.04±0.13, n=6), compared to control(pD2: 6.59±0.07, n=6, p<0.05). Also, Emax was improved by ataciguat treatment in the 2K-1C aorta (Emax: 81.0±1.0; n=6), and 2K aorta (Emax: 92.98±1.83; n=6), compared to control (Emax 2K-1C: 52.14 ±2.16, n=6; and Emax 2K: 76.07±4.35, n=6, p<0.05). In endothelial cell culture, treatment with ataciguat (0.1, 1 and 10 µM) decreased the superoxide anion formation induced by angiotensin II. Conclusions: our results suggest that ataciguat were able to improve endothelial function by superoxide anion inactivation.
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