Polyamines and epidermal growth factor in monocrotaline-induced pulmonary hypertension.
Multiple lines of evidence suggest that the polyamines, a family of low-molecular-weight organic cations with documented regulatory note in cell growth and differentiation, are involved with hyperplastic and hypertrophic responses of lung cells underlying hypertensive pulmonary vascular disease. Little is known, however, of the factor(s) initiating polyamine synthesis in pulmonary hypertension. This study tested the key aspects of the hypothesis that augmented polyamine synthesis, and attendent vascular structural alterations in monocrotaline (MCT)-treated rats can be ascribed to elaboration of an epidermal growth factor (EGF)-like mitogen. In lungs of rats treated 4 days previously with 60 mg/kg, EGF-like immunoreactivity was detected diffusely throughout perivascular regions. Intravenous administration of human recombinant EGF (125 pg/h) to rats for 1 wk was associated with medial thickening in pulmonary arteries between 100 and 200 microns in diameter, significant increases in lung polyamine contents, and a moderate elevation in mean pulmonary arterial pressure. These observations indicate that EGF can be detected in the lungs of MCT-treated rats and that exogenous EGF mimics some of the action of MCT on the rat lung. It is thus reasonable to speculate that an EGF-like mitogen may participate in the response to MCT in part through a polyamine-dependent mechanism.
Gillespie
M N
MN
University of Kentucky College of Pharmacology Division of Pharmacology and Toxicology Lexington 40536-0082.
Rippetoe
P E
PE
Haven
C A
CA
Shiao
R T
RT
Orlinska
U
U
Maley
B E
BE
Olson
J W
JW
D000818:Animals; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D008297:Male; D016686:Monocrotaline; D010947:Plants, Toxic; D011073:Polyamines / Q000378:metabolism*; D011651:Pulmonary Artery / Q000033:anatomy & histology / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids; D051381:Rats; D011919:Rats, Inbred Strains; D012674:Senecio
D011073:Polyamines; D011763:Pyrrolizidine Alkaloids; D004815:Epidermal Growth Factor; D016686:Monocrotaline