Western-style diet modulates contractile responses to phenylephrine differently in mesenteric arteries from senescence-accelerated prone (SAMP8) and resistant (SAMR1) mice

Abstract

The influence of two known cardiovascular risk factors, aging and consumption of a high-fat diet, on vascular mesenteric artery reactivity was examined in a mouse model of accelerated senescence (SAM). Five-month-old SAM prone (SAMP8) and resistant (SAMR1) female mice were fed a Western-type high-fat diet (WD; 8 weeks). Mesenteric arteries were dissected, and vascular reactivity, protein and messenger RNA expression, superoxide anion (O 2 (·-) ) and hydrogen peroxide formation were evaluated by wire myography, immunofluorescence, RT-qPCR, ethidium fluorescence and ferric-xylenol orange, respectively. Contraction to KCl and relaxation to acetylcholine remained unchanged irrespective of senescence and diet. Although similar contractions to phenylephrine were observed in SAMR1 and SAMP8, accelerated senescence was associated with decreased eNOS and nNOS and increased O 2 (·-) synthesis. Senescence-related alterations were compensated, at least partly, by the contribution of NO derived from iNOS and the enhanced endogenous antioxidant capacity of superoxide dismutase 1 to maintain vasoconstriction. Administration of a WD induced qualitatively different alterations in phenylephrine contractions of mesenteric arteries from SAMR1 and SAMP8. SAMR1 showed increased contractions partly as a result of decreased NO availability generated by decreased eNOS and nNOS and enhanced O 2 (·-) formation. In contrast, WD feeding in SAMP8 resulted in reduced contractions due to, at least in part, the increased functional participation of iNOS-derived NO. In conclusion, senescence-dependent intrinsic alterations during early stages of vascular senescence may promote vascular adaptation and predispose to further changes in response to high-fat intake, which may lead to the progression of aging-related cardiovascular disease, whereas young subjects lack the capacity for this adaptation.

Activation of α1A‐adrenoceptors desensitizes the rat aorta response to phenylephrine through a neuronal NOS pathway, a mechanism lost with ageing

“…However, conflicting results have been reported for nNOS expression. In tissues such as rat cerebral cortex and cerebellum (Siles et al, ) and mouse mesenteric arteries (Jiménez‐Altayó et al , ), mRNA levels for nNOS decline with ageing, whereas in rat aorta, no change in nNOS levels was observed with ageing (Lekontseva et al , ).…”

“…Ageing is associated with endothelial dysfunction (Vanhoutte et al , ) and a reduction in the expression of eNOS (Chou et al , ; Siles et al , ; Tanabe et al , ; Csiszar, ; Zanetti et al , ; Gong et al , ) and nNOS (Siles et al , ; Lekontseva et al , ; Jiménez‐Altayó et al , ). This would result in a decrease in NO bioavailability and the subsequent loss of NO‐mediated desensitization with ageing could have major consequences on the regulation of vascular tone and blood pressure.…”

Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment

“…For example, increased contractility in response to phenylephrine is described when eNOS is down-regulated in the vasculature [34,35]. Similarly, decreased vascular expression of nNOS is associated with a hyper-reactivity to phenylephrine [36]. Therefore, alterations in the expression of NOS isoforms might explain the increase in phenylephrine and 5-HT-induced contractions in fluoxetine-treated rats.…”

Stenosis coexists with compromised α1-adrenergic contractions in the ascending aorta of a mouse model of Williams-Beuren syndrome

“…www.nature.com/scientificreports www.nature.com/scientificreports/ Measurement of aortic oxidative stress. The oxidative fluorescent dye dihydroethidium (DHE; Sigma-Aldrich) was used to evaluate in situ production of superoxide anion in non-fixed 14 μm-thick aortic sections, as described 41 . Quantitative analysis of DHE-derived fluorescence in images obtained using a laser-scanning confocal microscope (×20 objective; Olympus FluoView 1000; Olympus, Shinjuku, Tokio, Japan) was performed with ImageJ 1.51j8 software.…”

“…Segments (2 mm) of the ascending thoracic aorta were set up on an isometric wire myograph (model 410 A; Danish Myo Technology, Aarhus, Denmark) filled with KHS (37 °C; 95% O 2 and 5% CO 2 ), as described 42 . Optimal tension was assessed in preliminary experiments by subjecting arterial segments to different resting tensions and challenging with 100 mM KCl 41,43 . The optimal tension of the ascending aorta was the same for WT and CD mice (5 mN).…”