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Published on: February 11, 2017
Growth factor expression and effects of amrinone in monocrotaline-induced pulmonary hypertension in rats
G H Burch1, L R Jensen, J Pappas
1Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, 84113, USA.
Abstract:
Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) have been implicated in myointimal proliferative arteriopathy, a lesion seen in monocrotaline-induced pulmonary hypertension (MIPH). The purpose of this study was to examine the expression of PDGF and bFGF in the lungs of rats given monocrotaline and to examine the effects of amrinone on the hearts and lungs of these rats. Twenty-four 26-day-old rats were randomized to receive either monocrotaline (approximately 3.6 mg/kg/d) or no monocrotaline and concomitantly to receive either amrinone (100 mg/kg/d) or no amrinone for 21 days. Lungs were examined for immunohistochemical evidence of PDGF and bFGF, and hearts were examined for effects of pulmonary hypertension and amrinone. Immunohistochemical staining of lungs showed no evidence of PDGF except in bronchioles. bFGF staining was similar between groups (no monocrotaline 25%, monocrotaline 27%, monocrotaline and amrinone 22%), and the staining was confined to the arterial walls. Rats given monocrotaline showed significantly greater right ventricular (RV) weight (0.13 +/- 0.02 g versus 0.23 +/- 0.04 g [mean +/- SD], P < 0.001), right ventricular/left ventricular (RV/LV) weight ratio (0.29 +/- 0.06 versus 0.59 +/- 0.1, P < 0.001), and lung/body weight ratio (0.006 +/- 0.001 versus 0.01 +/- 0.003, P < 0.05) than controls. Rats given monocrotaline and amrinone were not significantly different from rats given only monocrotaline with regard to RV weight, RV/LV weight ratio, or lung/body weight ratio. We conclude that the vasculopathy seen in MIPH is not associated with the presence of PDGF or bFGF, suggesting that other growth factors may mediate this process. The course of MIPH is not altered by amrinone.
Insights
This study found that platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are not associated with myointimal proliferative arteriopathy in monocrotaline-induced pulmonary hypertension (MIPH) in rats. Amrinone did not alter the course of MIPH.
Area of Science:
- Cardiovascular Research
- Pulmonary Hypertension
- Vascular Biology
Background:
- Myointimal proliferative arteriopathy is a key lesion in monocrotaline-induced pulmonary hypertension (MIPH).
- Platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) have been suggested to play a role in this condition.
Purpose of the Study:
- To investigate the expression of PDGF and bFGF in the lungs of rats with MIPH.
- To evaluate the therapeutic effects of amrinone on the cardiac and pulmonary manifestations of MIPH.
Main Methods:
- Rats were administered monocrotaline and/or amrinone for 21 days.
- Immunohistochemistry was used to detect PDGF and bFGF in lung tissue.
- Cardiac and lung weights were measured to assess the severity of pulmonary hypertension.
Main Results:
- PDGF was not detected in the lungs, except in bronchioles.
- bFGF staining was observed in arterial walls and showed no significant difference between groups.
- Monocrotaline administration led to significant increases in right ventricular weight, RV/LV weight ratio, and lung/body weight ratio.
- Amrinone treatment did not significantly alter these parameters in monocrotaline-treated rats.
Conclusions:
- The vasculopathy in MIPH is not associated with PDGF or bFGF, suggesting other growth factors mediate the process.
- Amrinone does not appear to alter the progression or severity of MIPH in this rat model.
