title: ERK1/2-mediated vasoconstriction normalizes wall stress in small mesenteric arteries during NOS inhibition in vivo.
abstract: As in essential hypertension, chronic nitric-oxide synthase (NOS) inhibition leads to hypertrophic remodeling in conduit and muscular arteries and inward eutrophic remodeling in small resistance arteries with activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in both vessel types. The authors tested the hypothesis that this remodeling heterogeneity could be related to distinct vasoreactivity patterns in small and larger arteries, with a vessel-specific function of ERK1/2 signaling. Using intravital microscopy in rats we have demonstrated that acute NOS inhibition (l-NA injection, 100 mg/kg) produced vasoconstriction of small mesenteric arteries. Consequently, the calculated in vivo wall stress was not significantly modified, despite the local rise in pressure. This could explain the lack of vascular protein synthesis elevation in vivo, an early index of hypertrophy. Inhibition of ERK1/2 activation with PD98059 blunted mesenteric artery contractions. Femoral arteries did not contract and were thus submitted to an enhanced wall stress and underwent hypertrophic remodeling in chronic conditions. In conclusion, the heterogeneous vascular remodeling in the l-NAME model is associated with a heterogeneous vasoconstriction response to acute NOS inhibition. Indeed, in contrast to larger arteries, l-NA-induced vasoconstriction in small arteries normalized wall stress and prevented early signs of hypertrophy. The results also suggest that ERK1/2 is a signaling element in NOS inhibition-induced vasoconstriction of small arteries in vivo.
authors.affiliation: Université de Montréal, Canada.
authors.forename: Daphné
authors.initials: D
authors.lastname: Girardot
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Demeilliers
authors.forename: Denis
authors.initials: D
authors.lastname: deBlois
authors.forename: Pierre
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D019001:Nitric Oxide Synthase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester