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Title: Effects of resveratrol on hypertension and resistance arteries in the Spontaneously Hypertensive Rat
Authors: Behbahani, John
Supervisor: Anderson, Hope (Pharmacy)
Examining Committee: Burczynski, Frank (Pharmacy) Netticadan, Thomas (Physiology)
Graduation Date: October 2010
Keywords: Hypertension
Issue Date: 12-Aug-2010
Abstract: Hypertension is accompanied by structural and mechanical abnormalities in resistance arteries. The effects of resveratrol, a phenolic phytoalexin found naturally in various foods, on systolic blood pressure and resistance artery structure and stiffness were assessed in spontaneously hypertensive rats (SHRs). Vascular geometry and mechanical properties of pressurized mesenteric resistance arteries were calculated from media and lumen dimensions measured using pressure myography. Compared to normotensive Wistar-Kyoto (WKY) rats, resistance arteries from SHRs displayed remodeling with narrowed lumen diameters (246.2±21.0 vs. 308.1±14.3 μm, p<0.05), thickened media widths (39.8±4.6 vs. 28.5±2.7 μm, p<0.05) and augmented media-to-lumen ratios (17.7±2.6 vs. 9.3±1.0, p<0.05). Calculations of remodeling and growth indices revealed that SHR vessels underwent mostly eutrophic remodeling. Systolic blood pressure was elevated in 20-week-old SHR versus WKY rats (219±6 vs. 155±6 mmHg, p<0.01) and was unaffected by resveratrol (2.5 mg/Kg/d). In SHRs, resveratrol treatment attenuated eutrophic remodeling and normalized increased vessel compliance (p<0.01) as determined by a restorative leftward shift in the stress-strain curve of SHR arteries (p<0.01). Resveratrol treatment restored stiffness in SHRs (4.2±0.4 vs. 6.6±0.5, p<0.05) through the normalization of vessel geometry. Immunoblotting revealed that resveratrol negated typical pronounced ERK1/2 signaling in SHR arteries. Thus, the results of this study suggest that resveratrol restores vascular mechanical properties in SHRs and attenuates remodeling. Furthermore the attenuation of remodeling in SHR arteries with resveratrol treatment is associated with the inhibition of ERK1/2 activity.
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