Signaling of angiotensin II-induced vascular protein synthesis in conduit and resistance arteries in vivo.
BACKGROUND
From in vitro studies, it has become clear that several signaling cascades are involved in angiotensin II-induced cellular hypertrophy. The aim of the present study was to determine some of the signaling pathways mediating angiotensin II (Ang II)-induced protein synthesis in vivo in large and small arteries.


METHODS
Newly synthesized proteins were labeled during 4 hours with tritiated leucine in conscious control animals, or animals infused for 24 hours with angiotensin II (400 ng/kg/min). Hemodynamic parameters were measure simultaneously. Pharmacological agents affecting signaling cascades were injected 5 hours before the end of Ang II infusion.


RESULTS
Angiotensin II nearly doubled the protein synthesis rate in the aorta and small mesenteric arteries, without affecting arterial pressure. The AT1 receptor antagonist Irbesartan antagonized the actions of Ang II. The Ang II-induced protein synthesis was associated with increased extracellular signal-regulated kinases (ERK)1/2 phosphorylation in aortic, but not in mesenteric vessels. Systemic administration of PD98059, an inhibitor of the ERK-1/2 pathway, produced a significant reduction of protein synthesis rate in the aorta, and only a modest decrease in mesenteric arteries. Rapamycin, which influences protein synthesis by alternative signaling, had a significant effect in both vessel types. Rapamycin and PD98059 did not alter basal protein synthesis and had minimal effects on arterial pressure.


CONCLUSIONS
ERK1/2 and rapamycin-sensitive pathways are involved in pressure-independent angiotensin II-induced vascular protein synthesis in vivo. However, their relative contribution may vary depending on the nature of the artery under investigation.
Daigle
Christine
C
Faculty of Pharmacy, Université de Montréal, PO Box 6128, Station centre-ville, Montréal, Québec, H3C 3J7 Canada. christine.daigle@aventis.com
Martens
Fabrice M A C
FM
Girardot
Daphné
D
Dao
Huy Hao
HH
Touyz
Rhian M
RM
Moreau
Pierre
P
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D000077405:Irbesartan; D007930:Leucine / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D005419:Flavonoids; D013777:Tetrazoles; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D007930:Leucine; D000077405:Irbesartan; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus