L-NAME-induced hypertension leads to hypertrophic remodeling in large arteries and to eutrophic remodeling (decreased internal diameter without changing cross sectional area) in small arteries. During eutrophic remodeling, smooth muscle cells are expected to reorganize their cytoskeleton and to alter the signaling pathways that regulate contractile protein activation and function. Focal adhesions, which offer a structural link between the actin cytoskeleton and the extracellular matrix elements, are composed of numerous structural and regulatory proteins such as vinculin and p140mDia.

Our objective was to measure the time course expression of proteins implicated in the structural (vinculin) and regulatory formation (p140mDia) of focal adhesions in a model of eutrophic remodeling of resistance arteries and compare the results with a model of hypertrophic remodeling.

Male Wistar rats were treated with L-NAME at a dose of 50 mg/kg/day during 1, 3, 6 and 24 hours, and 3, 7 and 14 days. Another group of rats received angiotensin II by osmotic pumps at a dose of 200 ng/kg/day during the same time course. A third group of rats served as control. Mesenteric arteries (excluding the superior mesenteric artery) were harvested and used for measurement of protein expression by western immunoblotting.

RESULTS: in mesenteric arteries, vinculin expression decreased during 1 to 6 hours of L-NAME administration (1 h: 18,7±4,3%, 3 h: 34,0±8,6%, 6 h: 35,8±6,9%; p<0,05). In angiotensin II-treated rats, vinculin expression was also decreased from 3 h to 3 days (3 h: 38,6±10,4%, 6 h: 45±8,8%, 24 h: 34,7±12,7%, 3 days: 36,6±7,6%; p<0.05). In contrast, p140mDia expression was reduced only at day 14 in L-NAME treated (34.7±3,5%; p<0,05), and was unchanged by Ang II administration. In resistance arteries, vinculin is reduced early during both eutrophic and hypertrophic remodeling, suggesting that focal adhesions may be reduced during hypertension-induced remodeling, irrespective of its type. In contrast, the regulatory protein (p140mDia) seemed only involved in eutrophic remodeling, albeit at a later stage of the remodeling process.

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