Effect of fasudil on hypoxic pulmonary hypertension and right ventricular hypertrophy in rats.

Abstract

OBJECTIVE:

To investigate whether right ventricular hypertrophy in hypoxic pulmonary hypertension (HPH) rats could be prevented by treatment with Rho kinase inhibitor fasudil.

METHODS:

The rat model of pulmonary hypertension was established by exposing rats to normobaric intermitent hypoxia [(10 ± 0.5)% O2]. Twenty-four Spraque-Dawley male rats were randomly divided into control group, hypoxic model group and hypoxia with fasudil groups (n=8 each). The mean pulmonary arterial pressure (mPAP), and right ventricle hypertrophy index (RVHI) were measured. Ultrastructure of the right ventricular myocardial cells was observed under transmission electron microscope (TEM).

RESULTS:

The level of mPAP (31.38 ± 1.98) mmHg and RVHI (0.47 ± 0.03) were significantly higher in the hypoxic model group than (15.25 ± 0.91) mmHg and (0.25 ± 0.02) in control group respectively (P<0.01). Transmission electron microscope (TEM) revealed the model group right ventricular mitochondria increased significantly, swelling, cristae blurred, lost, heart muscle Siming dark band was not clear. The level of mPAP (16.63 ± 1.53) mmHg and RVHI (0.27 ± 0.02) were significantly lower in fasudil treatment group than in model group respectively (P<0.01). After the intervention of fasudil right ventricular myocardial injury was significantly reduced.

CONCLUSIONS:

Fasudil may partly prevent and reverse the development of pulmonary hypertension and right ventricular hypertrophy and myocardial cell injury.

• Authors: Xing-Zhen Sun, Shu-Yan Li, Xiang-Yang Tian, Qing-Quan Wu
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 8 Pg. 9517-21 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26464714 (Publication Type: Journal Article)

Chemical References

• Protein Kinase Inhibitors
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives, pharmacology)
• Animals
• Disease Models, Animal
• Heart (drug effects)
• Hypertension, Pulmonary (pathology)
• Hypertrophy, Right Ventricular (pathology)
• Hypoxia (complications)
• Male
• Microscopy, Electron, Transmission
• Myocardium (ultrastructure)
• Protein Kinase Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley