Increased EGF binding and EGFR mRNA expression in rat aorta with chronic administration of pressor angiotensin II.
This study examines the changes in the mRNA expression of epidermal growth factor (EGF), EGF receptor (EGFR), platelet derived growth factor (PDGF-B), and transforming growth factor beta (TGF-beta 1) before and after sustained pressor infusion of angiotensin II (Ang II) for 4 weeks. A threefold increase occurred in the levels of EGFR mRNA (17,240 +/- 827 vs 6403 +/- 1372 units, P less than 0.01) and TGF-beta 1 mRNA (1644 +/- 584 vs 475 +/- 30 units, P less than 0.01) only in the aorta and not in the heart and kidney tissues. This increase in both of the above mRNA transcripts highly correlated (r = 0.96 and 0.92, P less than 0.01) with the elevation of blood pressure. The specific binding of 125I-labeled EGF to aortic membranes also increased (11,429 +/- 728 vs 8630 +/- 420 cpm/mg protein, P less than 0.05) with a parallel increase in the protein tyrosine kinase activity of the membranes indicating that the enhanced EGFR mRNA expression resulted in increased activity of a functional receptor. No significant changes were observed in either EGF mRNA or PDGF-B mRNA levels. These findings suggest that EGFR and TGF-beta 1 participate in the long-term progressive pressor response to Ang II and thus potentially in the progression and the maintenance of chronic hypertension.
Sambhi
M P
MP
Department of Medicine, Veterans Administration Medical Center, Sepulveda, California.
Swaminathan
N
N
Wang
H
H
Rong
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D004815:Epidermal Growth Factor; D066246:ErbB Receptors