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R. M. Touyz, C. Deschepper, Q. N. Diep, J. B. Park, G. He, E. L. Schiffrin, P-303: In vivo inhibition of ERK1/2-dependent signaling pathways improves vascular function in SHR, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 130A, https://doi.org/10.1016/S0895-7061(01)01474-1
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Abstract
Extracellular signal-regulated kinases (ERK1/2) influence vascular smooth muscle cell growth and contractility, important factors in blood pressure regulation. This study was designed to investigate whether short-term in vivo inhibition of the ERK1/2 pathway influences vascular function and blood pressure in SHR. SHR (6/group) and WKY (5/group) were injected subcutaneously with either PD98059, selective MEK1/2 inhibitor (20μg/g body weight), or vehicle. Blood pressure was measured by tellemetry for 24 hours after injection. Rats were then killed and small mesenteric arteries mounted as pressurized systems for morphometric analysis and assessment of endothelial function and Ang II-induced contractility. ERK1/2 phosphorylation was measured by Western blot assays using protein extracts from small mesenteric arteries. In vivo MEK1/2 inhibition significantly decreased (p<0.01) ERK1/2 phosphorylation in both groups, with greater effects in SHR than WKY. In SHR, PD98059 improved Ach-induced relaxation (98% vs 62%, PD98059 vs vehicle) and decreased Ang II-induced contraction by 35%. In PD98059-treated WKY, Ang II-stimulated contraction was only slightly reduced (15%). Vascular structure and blood pressure were not significantly altered by PD98059 in either group. In conclusion short-term in vivo inhibition of MEK1/2 improves endothelial function and vascular contractility in resistance arteries of SHR, suggesting a role for ERK1/2-dependent signaling pathways in altered vascular function in genetically hypertensive rats.
