[Impact of hydrogen sulfide donor on pulmonary vascular structure and vasoactive peptides in rats with pulmonary hypertension induced by high pulmonary blood flow].
OBJECTIVE
To explore the impact of hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS), on pulmonary vascular structure and vasoactive peptides in rats with pulmonary hypertension induced by high pulmonary blood flow.


METHODS
Thirty-two male Wistar rats, weighing 120-140 g, were randomly divided into shunt group (n=8), shunt + NaHS group (n=8), sham group (n=8), and sham + NaHS group (n=8). Rats in shunt group and shunt + NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. In the sham group and sham + NaHS group, rats experienced the same experimental processes except the shunting procedure. Rats in shunt + NaHS group and sham + NaHS group were intraperitoneally injected with an exogenous H2S donor--NaHS, at a dose of 56 micromol/(kg x d). Meanwhile, rats in shunt group and sham group were injected with the same volume of physiological saline. After 11 weeks of experiment, systolic pulmonary artery pressure (SPAP) of each rat was evaluated by using a right cardiac catheterization procedure. Heart tissues were separated as right ventricular (RV) and left ventricular plus septum (LV + SP), and the ratio of RV to LV + SP [RV/(LV + SP)] was calculated. The morphologic changes including micro-and ultra-structural changes of pulmonary arteries of rats were observed under optical microscope and electro-microscope, respectively. The percentage of muscular artery (MA) in small pulmonary arteries was calculated. The change of relative medial thickness (RMT) of pulmonary arteries was examined. H2S concentration in plasma was evaluated by modified sulfide electrode method. Endothelin-1 (ET-1), atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), and proadrenomedullin peptide (PAMP) were calculated by radioimmunoassay kit.


RESULTS
After 11 weeks of shunt, compared with sham group, SPAP increased by 48.63% (P < 0.01 ) and RV/ (LV + SP) increased by 21.95% (P < 0.01). Plasma H2S decreased significantly (P < 0.01). The percentage of MA increased significantly (P < 0.01); RMT increased significantly (P < 0.01). The changes of ultra-structure of pulmonary arteries showed that endothelial cells became swollen and desquamation, internal elastic lamina became irregular, and smooth muscular cells increased in size, showing synthetic phenotype. After the rats with shunt was administered with NaHS for 11 weeks, plasma H2S increased significantly (P < 0.01). SPAP decreased by 19.82% and RV/(LV + SP) decreased by 7.31% (P < 0.01). The percentage of MA decreased significantly and RMT decreased significantly (P < 0.01). The changes of ultra-structure of the pulmonary arteries showed lighten significantly. Plasma ET-1, ANP, and CGRP decreased significantly (all P < 0.01), whereas PAMP increased significantly than that of shunt group (P < 0.01).


CONCLUSIONS
The reduced production of endogenous H2S is one of mechanism of pulmonary hypertension and pulmonary vascular structure remodeling in rats with high pulmonary blood flow. H2S plays an important regulatory effect on vasoactive peptide ET-1,+ ANP, CGRP and PAMP.
Li
Xiao-hui
XH
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Du
Jun-bao
JB
Tang
Chao-shu
CS
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D006862:Hydrogen Sulfide / Q000097:blood*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000473:pathology; D008168:Lung / Q000098:blood supply; D008297:Male; D010455:Peptides / Q000097:blood; D011652:Pulmonary Circulation / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology*
D019332:Endothelin-1; D010455:Peptides; D013440:Sulfides; D009320:Atrial Natriuretic Factor; C025451:sodium bisulfide; D015740:Calcitonin Gene-Related Peptide; D006862:Hydrogen Sulfide