Arterial epidermal growth factor receptor expression in deoxycorticosterone acetate-salt hypertension.
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 micromol/L] contraction) compared with aorta from sham rats (4+/-2%). The EGFR tyrosine kinase-specific inhibitors 4,5-dianilinophthalimide (10 micromol/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.
Northcott
C
C
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317, USA.
Florian
J A
JA
Dorrance
A
A
Watts
S W
SW
D000818:Animals; D001158:Arteries / Q000502:physiology*; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000008:administration & dosage / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D012982:Sodium, Dietary; D003900:Desoxycorticosterone; D066246:ErbB Receptors