Peripheral and Cerebral Resistance Arteries in the Spontaneously Hypertensive Heart Failure Rat: Effects of Stilbenoid Polyphenols

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.

Regular Black Bean Consumption Is Necessary to Sustain Improvements in Small-Artery Vascular Compliance in the Spontaneously Hypertensive Rat

“…Vascular compliance, the ability of a vessel to buffer changes in pressure [19], was measured by plotting the relationship between media stress and media strain [20] for the mesenteric resistance arteries. There was a distinct separation of the stress-strain curves among the four animal groups.…”

“…Similar to Phase 1, SHR gained weight during the 8 weeks of black bean Unlike vascular compliance, incremental elastic modulus depends upon the stiffness of the vessel wall components independent of vessel geometry [19]. When incremental elastic modulus is plotted against media stress, the slope of elastic modulus vs. stress indicates the stiffness of wall components such as elastin, collagen, and SMC [20]. There were no differences in the slope of the elastic modulus vs. media stress among the four groups (Figure 3c,d), despite there being differences in arterial compliance.…”

Gnetol, a Resveratrol Derivative Ameliorates Malathion-Induced Neurotoxicity through Modulating Lysosomal Membrane Permeabilization in N2a Cells

“…Gnetol potential activates AMP-activated protein kinase (AMPK) and ERK directed vascular flexibility in rat spontaneous hypertensive heart failure model compared with other Stilbenoid derivates [31,32]. Resveratrol, a potential activator of SIRT1 inhibits aging disease like AD by mimic caloric restriction in animal models [33].…”

Dietary Polyphenols Targeting Arterial Stiffness: Interplay of Contributing Mechanisms and Gut Microbiome-Related Metabolism

“…Resveratrol and related stilbenoids pterostilbene and gnetol attenuate the increase in media-to-lumen ratio and wall component stiffness observed in a rat model of spontaneously hypertensive heart failure. However, the authors could not demonstrate a role of AMPK or extracellular signal-regulated kinases (ERK) herein [182]. In contrast, an attenuation of the vascular geometry remodeling process and ERK-signaling by resveratrol, rather than a direct effect on arterial wall stiffness, has been observed in spontaneously hypertensive rats [183].…”