[Effect of a new gasotransmitter, hydrogen sulfide, on collagen remodeling of pulmonary artery under hypoxia].
OBJECTIVE
To study the modulatory effect of hydrogen sulfide (H(2)S) on the accumulation of collagen type I and type III in the wall of pulmonary small artery during hypoxic pulmonary vascular remodeling.


METHODS
Nineteen male Wistar rats were randomly divided into a control group (n = 6), a hypoxic group (n = 7) and a hypoxia + NaHS group (n = 6). Hypoxic challenge was performed everyday for 21 days. NaHS solution was injected peritoneally everyday before hypoxia challenge for rats in the hypoxia + NaHS group. After 21 days of hypoxia, the mean pulmonary artery pressure was measured by pulmonary artery catheterization. The weight ratio of right ventricle to left ventricle + septum [RV/(LV + SP)] was also measured. The plasma level of H(2)S was determined by methylene blue spectrophotometric method. The expression of collagen type I and type III in pulmonary small arteries were detected by immunohistochemistry. The expression of procollagen type I and type III mRNA in pulmonary small arteries were detected by in situ hybridization.


RESULTS
(1) Compared with the control group, the mPAP increased by 46% (P < 0.01), the weight ratio of RV/(LV + SP) increased by 41% and the plasma level of H(2)S decreased by 36% for rats in the hypoxia group (P < 0.01). Compared with the hypoxia group, the mPAP decreased by 31% (P < 0.01), the weight ratio of RV/(LV + SP) decreased by 24% and the plasma level of H(2)S increased by 65% (P < 0.01) for rats in the hypoxia + NaHS group. (2) Expression of collagen type I in small and median pulmonary arteries of the three groups: compared with rats in the control group, collagen type I expression increased by 81% and 62% respectively for rats in the hypoxia group (P < 0.01); compared with rats in the hypoxia group, the expression decreased by 32% and 18% respectively for rats in the hypoxia + NaHS group (P < 0.01). (3) Expression of procollagen type I mRNA in small and mid pulmonary arteries of the three groups: compared with rats in the control group, the expression increased by 49% and 68% respectively (P < 0.01) for rats in the hypoxia group; compared with rats in the hypoxia group, the expression decreased by 31% and 33% respectively for rats in the hypoxia + NaHS group (P < 0.01). (4) Expression of collagen type III in small pulmonary arteries of the three groups: compared with rats in the control group, the expression increased by 84% for rats in the hypoxia group (P < 0.01); compared with rats in the hypoxia group, the expression decreased by 37% for rats in the hypoxia + NaHS group (P < 0.01). Compared with rats in the control group, the expression of collagen type III in median pulmonary arteries increased by 38% in the hypoxia group (P < 0.01), while there was no significant difference between the hypoxia group and the hypoxia + NaHS group. (5) Expression of procollagen type III mRNA in small and median pulmonary arteries of the three groups: compared with rats in the control group, the expression increased by 53% and 17% respectively (P < 0.01) for rats in the hypoxia group; compared with rats in the hypoxia group, the expression decreased by 45% and 33% respectively for rats in the hypoxia + NaHS group (P < 0.01).


CONCLUSIONS
In the process of hypoxic pulmonary vascular collagen remodeling in rats, H(2)S could inhibit the abnormal accumulation of collagen type I and type III in the wall of pulmonary small arteries. This effect may be one of the mechanisms by which H(2)S ameliorates hypoxic pulmonary vascular remodeling.
Zhang
Chun-yu
CY
Department of Pediatric, Peking University First Hospital, Beijing 100034, China.
Du
Jun-bao
JB
Yan
Hui
H
Tang
Chao-shu
CS
D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D006862:Hydrogen Sulfide