Abstract：Objective Endogenous hydrogen sulfide (H2S), a novel gasotransmitter in cardiovascular regulation, plays an important protective role in the development and progression of atherosclerosis (AS). This study was designed to explore the effects of H2S donor on the production of adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in AS rats. Methods Male Sprague-Dawley rats were randomly divided into control group (n=10), AS group (n=10), and AS+NaHS group (n=10). Rats in the AS and AS+NaHS groups were given 3-day intraperitoneal injections of vitamin D3 and 8-week high-fat diet to induce AS, and the rats in the AS+NaHS group were intraperitoneally injected with H2S donor NaHS. Oil red O staining was applied to detect changes in the areas of the atherosclerotic plaques in the aortic root and the coronary artery;sulfide-sensitive electrode method was used to measure the plasma concentration of H2S. ADM and ANP levels in plasma were determined by radioimmunoassay. Results Compared with the control group, marked atherosclerotic plaques were observed in the aortic root and the coronary artery in AS rats. Moreover, plasma H2S level decreased significantly, ADM level increased, and ANP level decreased significantly in AS rats (P2S donor NaHS for 8 weeks, the above changes in AS rats were reversed, demonstrated by significantly reduced areas of the atherosclerotic plaques in both the aortic root and the coronary artery, significantly increased plasma H2S level, significantly decreased plasma ADM level, and significantly increased plasma ANP level (PConclusions H2S plays an important regulatory effect on vasoactive peptides ADM and ANP in AS rats.
LI Wei,DU Jun-Bao,JIN Hong-Fang. Effects of hydrogen sulfide donor on production of adrenomedullin and atrial natriuretic peptide in rats with atherosclerosis[J]. CJCP, 2015, 17(10): 1119-1123.
Herouvi D, Karanasios E, Karayianni C, et al. Cardiovascular disease in childhood:the role of obesity[J]. Eur J Pediatr, 2013, 172(6):721-732.
[2]
Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults[J]. N Engl J Med, 1998, 338(23):1650-1656.
[3]
Yu XH, Cui LB, Wu K, et al. Hydrogen sulfide as a potent cardiovascular protective agent[J]. Clin Chim Acta, 2014, 437:78-87.
Wang Y, Zhao X, Jin H, et al. Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice[J]. Arterioscler Thromb Vasc Biol, 2009, 29(2):173-179.
[6]
Mani S, Untereiner A, Wu L, et al. Hydrogen sulfide and the pathogenesis of atherosclerosis[J]. Antioxid Redox Signal, 2014, 20(5):805-817.
[7]
Qiao W, Chaoshu T, Hongfang J, et al. Endogenous hydrogen sulfide is involved in the pathogenesis of atherosclerosis[J]. Biochem Biophys Res Commun, 2010, 396(2):182-186.
[8]
Xu S, Liu Z, Liu P. Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis[J]. Int J Cardiol, 2014,172(2):313-317.
[9]
Lynn EG, Austin RC. Hydrogen sulfide in the pathogenesis of atherosclerosis and its therapeutic potential[J]. Expert Rev Clin Pharmacol, 2011, 4(1):97-108.
[10]
Huang ZY, Yang PY, Almofti MR, et al. Comparative analysis of the proteome of left ventricular heart of arteriosclerosis in rat[J]. Life Sci, 2004, 75(26):3103-3115.
[11]
Peh MT, Anwar AB, Ng DS, et al. Effect of feeding a high fat diet on hydrogen sulfide (H2S) metabolism in the mouse[J]. Nitric Oxide, 2014, 41:138-145.
[12]
Mani S, Li H, Untereiner A, et al. Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis[J]. Circulation, 2013, 127(25):2523-2534.
[13]
Cheung SH, Kwok WK, To KF, et al. Anti-atherogenic effect of hydrogen sulfide by over-expression of cystathionine gammalyase (CSE) gene[J]. PLoS One, 2014, 9(11):e113038.
[14]
Liu Z, Han Y, Li L, et al. The hydrogen sulfide donor, GYY4137, exhibits anti-atherosclerotic activity in high fat fed apolipoprotein E-/-mice[J]. Br J Pharmacol, 2013, 169(8):1795-1809.
Peter EA, Shen X, Shah SH, et al. Plasma free H2S levels are elevated in patients with cardiovascular disease[J]. J Am Heart Assoc, 2013, 2(5):e000387.
[17]
Altaany Z, Moccia F, Munaron L, et al. Hydrogen sulfide and endothelial dysfunction:relationship with nitric oxide[J]. Curr Med Chem, 2014, 21(32):3646-3661.
[18]
Baskar R, Sparatore A, Del Soldato P, et al. Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative inhibit rat vascular smooth muscle cell proliferation[J]. Eur J Pharmacol, 2008, 594(1-3):1-8.
[19]
Wang XH, Wang F, You SJ, et al. Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDLinduced inflammation in macrophage[J]. Cell Signal, 2013, 25(11):2255-2262.
[20]
Wen YD, Wang H, Kho SH, et al. Hydrogen sulfide protects HUVECs against hydrogen peroxide induced mitochondrial dysfunction and oxidative stress[J]. PLoS One, 2013, 8(2):e53147.
[21]
Watanabe T, Sato K, Itoh F, et al. Emerging roles for vasoactive peptides in diagnostic and therapeutic strategies against atherosclerotic cardiovascular diseases[J]. Curr Protein Pept Sci, 2013, 14(6):472-480.
[22]
Pan CS, Zhang J, Yu F, et al. Adrenomedullin ameliorates the development of atherosclerosis in apoE-/-mice[J]. Peptides, 2010, 31(6):1150-1158.
[23]
Nakayama M, Takahashi K, Murakami O, et al. Adrenomedullin in monocytes and macrophages:possible involvement of macrophage-derived adrenomedullin in atherogenesis[J]. Clin Sci (Lond), 1999, 97(2):247-251.
[24]
Gottsäter M, Ford LB, Ostling G, et al. Adrenomedullin is a marker of carotid plaques and intima-media thickness as well as brachial pulse pressure[J]. J Hypertens, 2013, 31(10):1959-1965.
[25]
De Vito P. Atrial natriuretic peptide:an old hormone or a new cytokine[J]? Peptides, 2014, 58:108-116.
[26]
Ichiki T1, Izumi R, Cataliotti A, et al. Endothelial permeability in vitro and in vivo:protective actions of ANP and omapatrilat in experimentalatherosclerosis[J]. Peptides, 2013, 48:21-26.
[27]
Larifla L, Déprez I, Pham I, et al. Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery[J]. J Gene Med, 2012, 14(7):459-467.
[28]
Gao P, Huang L. New insights into the role of natriuretic peptides in the regulation of apoptosis in cardiovascular system[J]. Saudi Med J, 2009, 30(5):595-604.
[29]
De Vito P, Incerpi S, Pedersen JZ, et al. Atrial natriuretic peptide and oxidative stress[J]. Peptides, 2010, 31(7):1412-1419.
