Arterial epidermal growth factor receptor expression in deoxycorticosterone acetate-salt hypertension

Abstract

Epidermal growth factor (EGF) causes contraction in arteries from deoxycorticosterone acetate (DOCA) - salt hypertensive rats but not in normotensive sham rats. We hypothesized that an increase in the number of EGF receptors (EGFRs) in arteries from DOCA-salt rats enables the observed contraction to EGF to occur. DOCA-salt rats had a systolic blood pressure >170 mm Hg, whereas all sham rats had a systolic blood pressure <125 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 (38±7% of maximal phenylephrine-induced [10 μmol/L] contraction) compared with aorta from sham rats (4±2%). The EGFR tyrosine kinase - specific inhibitors 4,5-dianilinophthalimide (10 μmol/L) and AG1478 (250 nmol/L) reduced contraction in aorta from DOCA-salt by 85±14% and 65±10%, respectively. EGFR mRNA in DOCA-salt aorta was increased 4.2-fold compared with that in sham aorta. However, Western analyses of membrane-enriched and whole-tissue lysate of aorta from sham and DOCA-salt revealed no statistical difference in the density of EGFR protein between sham and DOCA-salt aorta. These data refute our hypothesis and suggest that a change downstream of EGFR is responsible for enabling EGF-induced contraction in hypertension.