[Protective effects of rosiglitazone intervention on monocrotaline-induced pulmonary arterial hypertension in rats and related inflammatory mechanisms].

Abstract

OBJECTIVE:

To investigate the protective effects of rosiglitazone intervention on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and the possible mechanisms.

METHODS:

Thirty-two Sprague-Dawley rats were randomly divided into 4 groups: control group with a subcutaneous injection of normal saline. PAH group, high-dose and low-dose rosiglitazone intervention groups all with a subcutaneous injection of MCT and then gastric infusion of normal saline (1.5 ml/d), rosiglitazone (5, 2.5 mg·kg(-1)×d(-1)). At Day 21, the mean pulmonary arterial pressure (mPAP) was detected by right heart catheter. Then rats were sacrificed and their lungs extracted. Perivascular inflammation was scored with the subjective scale of 0 to 4. The tunica media thickness percentage of small pulmonary arteries (WT%) of rats was calculated. Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and monocyte chemotactic protein 1 (MCP-1) of lung tissue were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTS:

Compared with the PAH group ((37 ± 5) mm Hg (1 mm Hg = 0.133 kPa), 45.5% ± 5.5%), the mPAP and WT% of the high-dose ((27 ± 4) mm Hg, 13.1% ± 3.9%) and low-dose ((28 ± 4) mm Hg, 16.7% ± 1.7%) rosiglitazone intervention group were significantly lower (P < 0.01), but were still higher than those of the control group ((17 ± 3) mm Hg, 8.9% ± 2.3%) (P < 0.05 or P < 0.01). The perivascular inflammation score and levels of IL-6, TNF-α, MCP-1 of high-dose and low-dose rosiglitazone intervention groups were significantly lower than those of the PAH group (P < 0.01). Compared with the low-dose rosiglitazone intervention group, all the above indices of the high-dose rosiglitazone intervention group appeared much lower (P > 0.05).

CONCLUSION:

The protective effects of rosiglitazone against MCT-induced PH are correlated with drug dose and may be due to the inhibition of inflammation.

• Authors: Xiao-fang Wang, Wei-xuan Lu, Jun Guo, Guo Li, Yun-jian Zhang
• Journal: Zhonghua yi xue za zhi (Zhonghua Yi Xue Za Zhi) Vol. 92 Issue 30 Pg. 2144-7 (Aug 14 2012) ISSN: 0376-2491 [Print] China
• PMID: 23158281 (Publication Type: Journal Article)

Chemical References

• Thiazolidinediones
• Rosiglitazone
• Monocrotaline

Topics

• Animals
• Hypertension, Pulmonary (chemically induced, pathology, physiopathology)
• Inflammation (metabolism)
• Male
• Monocrotaline (adverse effects)
• Pulmonary Artery (pathology)
• Rats
• Rats, Sprague-Dawley
• Rosiglitazone
• Thiazolidinediones (pharmacology)