| Summary: | <p>Abstract</p> <p>Background</p> <p>From <it>in vitro </it>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 <it>in vivo </it>in large and small arteries.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Angiotensin II nearly doubled the protein synthesis rate in the aorta and small mesenteric arteries, without affecting arterial pressure. The AT<sub>1 </sub>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.</p> <p>Conclusion</p> <p>ERK1/2 and rapamycin-sensitive pathways are involved in pressure-independent angiotensin II-induced vascular protein synthesis <it>in vivo</it>. However, their relative contribution may vary depending on the nature of the artery under investigation.</p>
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