Growth factor expression and effects of amrinone in monocrotaline-induced pulmonary hypertension in rats.
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.
Burch
G H
GH
Department of Pediatrics, University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, Utah, 84113, USA.
Jensen
L R
LR
Pappas
J
J
Hammond
E H
EH
Banner
W
W
Shaddy
R E
RE
D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001980:Bronchi / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000187:drug effects; D011042:Poisons; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D010982:Platelet-Derived Growth Factor; D011042:Poisons; D014665:Vasodilator Agents; D016222:Fibroblast Growth Factor 2; D016686:Monocrotaline; D000676:Amrinone