Open AccessHydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats 1
Author(s) -
WU Shengying,
PAN Chunshui,
GENG Bin,
ZHAO Jing,
YU Fang,
PANG Yongzheng,
TANG Chaoshu,
QI Yongfen
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00283.x
Subject(s) - chemistry , alkaline phosphatase , calcification , calcium , endocrinology , medicine , aorta , biochemistry , biology , enzyme , organic chemistry
Aim: To investigate the role of the endogenous cystathionine γ‐synthase (CSE)/ hydrogen sulfide (H 2 S) pathway in vascular calcification in vivo. Methods: A rat vascular calcification model was established by administration of vitamin D3 plus nicotine (VDN). The amount of CSE and osteopontin (OPN) mRNA was determined by using semi‐quantitative reverse‐transcription polymerase chain reaction. The calcium content, 45 Ca 2+ accumulation and alkaline phosphatase (ALP) activity were measured. H 2 S production and CSE activity were measured. Results: von Kossa staining produced strong positive black/brown staining in areas among the elastic fibers of the medial layer in the calcified aorta. The calcium content, 45 Ca 2+ accumulation and ALP activity in calcified arteries increased by 6.77‐, 1.42‐, and 1.87‐fold, respectively, compared with controls. The expression of the OPN gene was upregulated ( P < 0.01). Expression of the CSE gene was downregulated. However, calcium content, 45 Ca 2+ uptake and ALP activity in the VDN plus NaHS group was lower than that in the VDN group. The content of calcium and 45 Ca 2+ accumulation and activity of ALP in the aorta were 34.8%, 40.75% and 63.5%lower in the low‐dosage NaHS group than in the VDN group, respectively ( P < 0.01), and the calcium content and deposition of 45 Ca 2+ and activity of ALP was 83.9%, 37.8 % and 46.2% lower in the aorta in the high‐dosage NaHS group than in the VDN group, respectively ( P < 0.01). The expression of the OPN gene was downregulated. Conclusion: The production of H 2 S, and CSE activity were decreased and CSE gene expression was downregulated in rats with vascular calcification. H 2 S can ameliorate vascular calcification, suggesting that the H 2 S/ CSE pathway plays a regulatory role in the pathogenesis of vascular calcification.