Epidermal growth factor augments reactivity to angiotensin II in the rat pulmonary circulation.
To determine if epidermal growth factor (EGF), a vascular smooth muscle mitogen exhibiting systemic vasoactivity, causes constriction or dilation of the pulmonary vascular bed, this study evaluated the actions of EGF in isolated, buffer-perfused rat lungs and in isolated rat pulmonary arteries. In perfused rat lungs with baseline vasomotor tone, EGF administered at bolus doses of 10(-9) to 3 x 10(-7) M failed to exert either constrictor or dilator actions or to promote edema formation as evidenced by a constant lung wet-to-dry-weight ratio. Elevation of baseline tone with either prostaglandin (PG)F2 alpha or angiotensin II also failed to unmask an effect of EGF on pulmonary vascular resistance. In contrast to these negative observations, pretreatment with 5 x 10(-8) M EGF consistently augmented pressor responses evoked by angiotensin II. Constrictor responses to potassium chloride and to PGF2 alpha were unaffected by EGF pretreatment. In isolated rat extrapulmonary arteries, EGF provoked contraction in 40% of the preparations studied. Responsive vessels exhibited maximal EGF-induced contractions that were approximately 25% of that associated with angiotensin II and were characterized by an ED50 of 7 x 10(-8) M. Relaxant activity of EGF could not be demonstrated in isolated arterial preparations with normal resting tone or with tone elevated by addition of norepinephrine to the tissue bath. Endothelial denudation also failed to unmask contractile or relaxant effects of EGF. Similar to its actions in isolated, perfused rat lungs, EGF potentiated contractions of isolated pulmonary arteries induced by angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Rippetoe
P E
PE
University of Kentucky A.B. Chandler Medical Center, College of Pharmacy, Division of Pharmacology and Toxicology, Lexington.
Olson
J W
JW
Altiere
R J
RJ
Pauly
T H
TH
Gillespie
M N
MN
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D004815:Epidermal Growth Factor