EGF receptor transactivation in angiotensin II and endothelin control of vascular protein synthesis in vivo.
Endothelin represents a necessary intermediate of angiotensin II-induced resistance artery remodeling in hypertension. Recent data suggest that epidermal growth factor receptors are rapidly transactivated by angiotensin II stimulation to mediate its growth-promoting effects. Because endothelin also transactivates epidermal growth factor receptors in vitro, we studied the contribution of epidermal growth factor receptor transactivation in the in vivo trophic actions of the upstream effector angiotensin II and its downstream mediator endothelin in rat mesenteric arteries. Twenty-six-hour infusion of angiotensin II (400 ng/kg per min) or endothelin (5 pmol/kg per min) via osmotic pumps significantly enhanced vascular protein synthesis. With angiotensin II, treatment with the inhibitor of epidermal growth factor receptor transactivation (AG1478, 0.5 mg/kg) produced a significant attenuation (P < 0.05) of protein synthesis. In contrast, AG1478 did not abrogate the elevation of protein synthesis induced by endothelin. In conclusion, angiotensin II-induced epidermal growth factor receptor transactivation seems to be involved in the recruitment of endothelin in the cascade leading to vascular protein synthesis, rather than in the effect of endothelin on small artery remodeling.
Beaucage
Pierre
P
Faculté de Pharmacie, Université de Montréal, Montréal, Canada.
Moreau
Pierre
P
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D016232:Endothelins / Q000008:administration & dosage; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006339:Heart Rate; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020032:Tyrphostins / Q000494:pharmacology
D016232:Endothelins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D020032:Tyrphostins; D000804:Angiotensin II; C101044:RTKI cpd; C483803:Egfr protein, rat; D066246:ErbB Receptors