Contribution of hydrogen sulfide and nitric oxide to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats
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It is well known that exercise training attenuates aortic remodeling and improves endothelial function in spontaneously hypertensive rats (SHR). However, the underlying molecular mechanism remains unclear. Hydrogen sulfide (H2S) and nitric oxide (NO), as two established physiologic messenger molecules, have important roles in the development of aortic remodeling and endothelial dysfunction in hypertensive animals and patients. In this work, it was found that exercise training had no significant effect on blood pressure, but effectively attenuated baroreflex dysfunction in SHR. Exercise training in SHR attenuated aortic remodeling and improved endothelium-mediated vascular relaxations of aortas in response to acetylcholine. Interestingly, exercise training in SHR restored plasma H2S levels and aortic H2S formation and enhanced levels of mRNA for cystathionine γ-lyase in aortas. Furthermore, exercise training in SHR resulted in augmentation of nitrite and nitrate (NOx) contents and reduction of asymmetric dimethylarginine contents of aortas, upregulation of dimethylarginine dimethylaminohydrolase 2, and phosphorylation of nitric oxide synthase 3, but had no significant effect on protein levels of NOS3. In addition, exercise training could effectively reduce malondialdehyde production and suppressed formation of O2 −, and OONO− in aortas of SHR through enhancing activities of superoxide dismutase and catalase, and suppressing NADPH oxidase activity. In conclusion, exercise training ameliorates aortic hypertrophy and endothelial dysfunction, possibly via restoring bioavailabilities of hydrogen sulfide and nitric oxide in SHR.
KeywordsExercise training Spontaneously hypertensive rats Aortic remodeling Endothelial dysfunction Hydrogen sulfide Nitric oxide
- 9.Shi YX, Chen Y, Zhu YZ, Huang GY, Moore PK, Huang SH, Yao T, Zhu YC (2007) Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 293:H2093–H2100PubMedCrossRefGoogle Scholar
- 38.Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, Vallance P (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 23:1455–1459PubMedCrossRefGoogle Scholar
- 41.Carballala S, Trujillob M, Cuevasantaa E, Bartesaghib S, Möllerc MN, Folkesf LK, García-Bereguiaíng MA, Gutiérrez-Merinog C, Wardmanf P, Denicolac A, Radib R, Alvarez B (2011) Reactivity of hydrogen sulfide with peroxynitrite and other oxidants of biological interest. Free Radic Biol Med 50:196–205CrossRefGoogle Scholar