Regulatory effect of hydrogen sulfide on vascular collagen content in spontaneously hypertensive rats.
The present study aimed to examine the regulatory effect of hydrogen sulfide (H2S) on vascular collagen remodeling in hypertensive rats. After 5 weeks of H2S donor treatment, tail blood pressure, the endogenous H2S production rate, levels of hydroxyproline and collagen type I, collagen type I protein expression in the thoracic aorta, [3H]thymidine ([3H]TdR) incorporation, [3H]proline incorporation, and [3H]hydroxyproline secretion in cultured vascular smooth muscle cells (VSMCs) were measured. We also examined the effects of NaHS on angiotensin II-induced mitogen-activated protein kinase (MAPK) activation and angiotensin II type 1 (AT1) receptor binding affinity. Vascular hydroxyproline and collagen type I levels were high, and collagen type I immunohistochemical staining in the thoracic aorta was strong in SHRs compared to Wistar Kyoto (WKY) rats. [3H]TdR and [3H]proline incorporation and [3H]hydroxyproline secretion were also higher in cultured VSMCs from SHR than those from WKY rats. However, vascular H2S production was lower in SHR compared with WKY rats. Treatment with NaHS increased vascular H2S production in SHRs, and partly reversed the changes in [3H]TdR and [3H]proline incorporation and [3H]hydroxyproline secretion. In cultured VSMCs, [3H]TdR and [3H]proline incorporation stimulated by angiotensin II was inhibited by incubation with NaHS. The inhibitory effect of NaHS on VSMC proliferation and collagen generation was stronger in the SHR than in the WKY group. Moreover, NaHS could dose-dependently decrease angiotensin II-induced MAPK activation. NaHS also decreased AT1 receptor binding as well as the binding affinity of the AT1 receptor. Thus, in SHRs, which demonstrated vascular remodeling and collagen accumulation, the endogenous H2S pathway is involved in the regulation of excess vascular collagen.
Zhao
Xia
X
Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
Zhang
Li-Ke
LK
Zhang
Chun-Yu
CY
Zeng
Xiang-Jun
XJ
Yan
Hui
H
Jin
Hong-Fang
HF
Tang
Chao-Shu
CS
DU
Jun-Bao
JB
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism / Q000493:pharmacokinetics; D006973:Hypertension / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000493:pharmacokinetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D024042:Collagen Type I; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D014316:Tritium; D000804:Angiotensin II; D011392:Proline; D006909:Hydroxyproline; D013936:Thymidine; D006862:Hydrogen Sulfide