Increased Epidermal Growth Factor Receptor Expression in Rat Aorta in Deoxycorticosterone Acetate-Salt Induced Hypertension/ATL>
Receptors and signal transduction
Epidermal growth factor (EGF) causes contraction in arteries from Deoxycorticosterone Acetate-Salt (DOCA) hypertensive rats but not in normotensive sham rats. We hypothesized that an increase in the number of EGF receptors (EGFR) in arteries from DOCA-salt rats enables the observed contraction to EGF to occur. All DOCA-salt rats had a systolic blood pressure (SBP) > 170 mm Hg, while all sham rats had a SBP < 135 mm Hg. Thoracic aorta were removed for measurement of isometric force, EGFR mRNA levels, and EGFR protein levels. EGF caused a significant contraction in endothelium-denuded aorta from DOCA-salt rats [(35 +/- 3% of maximal phenylephrine (PE, 10uM)-induced contraction)] as compared to aorta from sham rats (4+/-2%). EGFR tyrosine kinase specific inhibitors, 4,5-Dianilinophthalimide (10uM) and AG1478 (250 nM), reduced the contraction in aorta from DOCA-salt rats by 85 +/- 14% and 65+/- 10% respectively. The mRNA for EGFR in DOCA-salt aorta was increased 4.2 fold as compared to sham aorta. EGFR protein levels were examined using immunohistochemistry where specific binding was defined as binding which was quenched by a 10x concentration of neutralizing peptide. In 7 of 8 quantitative comparisons between aorta from DOCA-salt and sham rats, DOCA-salt aorta sections demonstrated greater specific binding than in sections of sham aorta. In the 7 positive comparisons, the difference in specific binding between DOCA-salt and sham sections ranged from 2.31 to 20.67 gray scale units (gsu) with an average of 9.18 gsu (figure). An increase in specific binding in aorta from DOCA-salt rats suggests the vessels have more EGFR that could facilitate the enhanced contractility to EGF in DOCA-salt aorta.