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(Hypertension. 2002;39:16.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Vessel-Specific Stimulation of Protein Synthesis by Nitric Oxide Synthase Inhibition

Role of Extracellular Signal–Regulated Kinases 1/2

Fabrice M.A.C. Martens; Bénédicte Demeilliers; Daphné Girardot; Christine Daigle; Huy Hao Dao; Denis deBlois; Pierre Moreau

From the Faculty of Pharmacy (F.M.A.C.M., B.D., D.G., C.D., H.H.D., P.M.) and the Department of Pharmacology, Faculty of Medicine (D.d.B.), Université de Montréal, Montréal, Canada. Dr Martens is now at University Hospital of Utrecht, Utrecht, the Netherlands.

Correspondence to Pierre Moreau, PhD, Assistant Professor, Faculty of Pharmacy, Université de Montréal, 2900 Edouard-Montpetit, Room R-313, PO Box 6128, Stn "Centre-ville," Montréal, Québec, H3C 3J7 Canada. E-mail Pierre.Moreau{at}Umontreal.CA

Although conduit arteries develop hypertrophy after chronic NO synthesis blockade, resistance arteries remodel without hypertrophy under the same conditions. Similar findings have been described in essential hypertension. We postulated that this regional difference may be related to a heterogeneous effect of endogenous NO on proliferation along the vascular tree. Newly synthesized proteins were radiolabeled in vivo with [³H]L-leucine in basal conditions and during NO synthase inhibition, with or without PD98059 (inhibitor of the extracellular signal–regulated kinases [ERK] 1/2). Blocking the generation of NO by 3 different L-arginine analogues increased protein synthesis by an average of 75% in the aorta, in association with enhanced ERK 1/2 phosphorylation. PD98059 significantly reduced L-arginine analogue–induced protein synthesis and ERK 1/2 phosphorylation, confirming the involvement of ERK 1/2 as an important signaling element. In small arteries, L-arginine analogues did not influence the extent of protein synthesis, although phosphorylation of ERK 1/2 was also enhanced. To determine the role of NO in a condition of enhanced protein synthesis, angiotensin II was infused for 24 hours. Angiotensin II augmented protein synthesis in mesenteric arteries and the aorta, and was additive to NO synthase blockade in the aorta. In conclusion, endogenous NO exerts a tonic inhibitory influence on aortic growth, with limited impact on small arteries in basal and hypertrophic conditions. This heterogeneous role of NO on vascular growth may explain the heterogeneity of vascular remodeling observed in essential hypertension, a condition associated with endothelial dysfunction.

Key Words: hypertrophy • nitric oxide • nitric oxide synthase • kinase • arteries • aorta

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