Abstract
Hypertension is associated with aberrant structure and mechanical properties of resistance arteries. We determined the effects of resveratrol, a non-flavonoid polyphenol found in foods such as red grapes, and structurally-similar analogues (pterostilbene and gnetol) on systolic blood pressure (SBP) and resistance arteries from the spontaneously hypertensive heart failure (SHHF) rat. SBP was elevated in 17-week-old SHHF vs. Sprague-Dawley rats (normotensive control; 194 ± 3 vs. 142 ± 6 mmHg, p < 0.01) and was unaffected by resveratrol, pterostilbene, or gnetol (2.5 mg/kg/d). Geometry and mechanical properties of pressurized mesenteric resistance arteries and middle cerebral arteries were calculated from media and lumen dimensions measured at incremental intraluminal pressures. SHHF arteries exhibited remodeling which consisted of augmented media-to-lumen ratios, and this was attenuated by stilbenoid treatment. Compliance was significantly reduced in SHHF middle cerebral arteries but not mesenteric arteries vis-à-vis increased wall component stiffness; stilbenoid treatment failed to normalize compliance and wall component stiffness. Our data suggest that neither AMPK nor ERK mediate stilbenoid effects. In conclusion, we observed arterial bed-specific abnormalities, where mesenteric resistance arteries exhibited remodeling and cerebral arteries exhibited remodeling and stiffening. Resveratrol, pterostilbene, and gnetol exhibited similar abilities to attenuate vascular alterations.
Highlights
Blood pressure is proportional to cardiac output and total peripheral resistance
We reported that the ability of resveratrol to attenuate increased compliance of mesenteric arteries in spontaneously hypertensive rat (SHR) was associated with complete normalization of ERK to WKY levels [33]
In mesenteric arteries from untreated spontaneously hypertensive heart failure (SHHF), the increase in media-to-lumen ratio and virtually unchanged media CSA indicate eutrophic remodeling, which is supported by the calculated remodeling and growth indices of 97.4% and 3.9%, respectively
Summary
Blood pressure is proportional to cardiac output and total peripheral resistance. Since resistance arteries by definition generate resistance to blood flow, and abnormalities of resistance arteries play a role in the pathogenesis and maintenance of hypertension in humans and experimental animals [1,2]. Given the importance of resistance arteries in determining blood pressure, we were intrigued by the notion that perhaps a bioactive component within grapes might be beneficial to microvascular health. This gave rise to our reported postulate that naturally-occurring stilbenoids, and in particular resveratrol, might be conferring the beneficial effects on microvascular function observed with increased fruit and vegetable consumption [17]. We examined the effects of resveratrol, pterostilbene and gnetol on blood pressure and microvasculature in the spontaneously hypertensive heart failure (SHHF) rat. We speculated that ERK was an important candidate mediator of stilbenoid effects
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