Sodium hydrosulfide alleviates pulmonary artery collagen remodeling in rats with high pulmonary blood flow

Heart Vessels. 2008 Nov;23(6):409-19. doi: 10.1007/s00380-008-1059-4. Epub 2008 Nov 27.

Abstract

This study aimed to explore the effect of sodium hydrosulfide (NaHS) on pulmonary artery collagen remodeling in rats with high pulmonary blood flow. Thirty-two Sprague-Dawley rats were randomly divided into a sham group, shunt group, sham + NaHS (an H2S donor) group, and shunt + NaHS group. After 11 weeks of shunting, mean pulmonary artery pressure (MPAP), relative median area (RMA) of pulmonary arteries, H2S concentration in lung tissues, plasma endothelin-1 (ET-1) levels, and ET-1 mRNA in lung tissues were investigated. Collagen I and collagen III were evaluated by immunohistochemistry. Hydroxyproline assay and Sirius-red staining were performed. Matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and connective tissue growth factor (CTGF) were evaluated by immunohistochemistry. After 11 weeks of shunting, rats showed a significant pulmonary hypertension and pulmonary artery collagen remodeling in association with a decrease in lung tissue H2S content. After NaHS treatment for 11 weeks, lung tissue H(2)S content was increased, whereas MPAP was attenuated and RMA was reduced. Meanwhile, pulmonary artery collagen I and collagen III protein expressions of intra-acinar pulmonary arteries were inhibited, but MMP-13/TIMP-1 ratio was augmented with a decreased plasma ET-1 content and lung tissue ET-1mRNA and CTGF expressions. The downregulation of H(2)S is involved in the development of pulmonary artery collagen remodeling induced by high pulmonary blood flow.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity / drug effects
  • Blood Flow Velocity / physiology*
  • Collagen Type I / drug effects
  • Collagen Type I / metabolism*
  • Collagen Type III / drug effects
  • Collagen Type III / metabolism*
  • Disease Models, Animal
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology
  • Immunohistochemistry
  • Male
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism*
  • Pulmonary Artery / physiopathology
  • Pulmonary Wedge Pressure / drug effects
  • Pulmonary Wedge Pressure / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfides / pharmacology*

Substances

  • Collagen Type I
  • Collagen Type III
  • Sulfides
  • sodium bisulfide