The Effects of Fermentation of Low or High Tannin Fava Bean-Based Diets on Glucose Response, Cardiovascular Function, and Fecal Bile Acid Excretion during a 28-Day Feeding Period in Dogs: Comparison with Commercial Diets with Normal vs. High Protein

We have shown that feeding dogs fava bean (FB)-based diets for 7 days is safe and FB flour fermentation with Candida utilis has the potential to decrease FB anti-nutritional factors. In the present study, the effects of 28-day feeding of 4 different FB-based test dog foods containing moderate protein (~27% dry matter (DM)) were compared with two commercial diets with normal protein (NP, grain-containing, ~31% DM protein) or high protein (HP, grain-free, ~41% DM protein). Health parameters were investigated in beagles fed the NP or HP diets or using a randomized, crossover, 2 × 2 Latin square design of the FB diets: unfermented high-tannin (UF-HT), fermented high-tannin (FM-HT), unfermented low-tannin (UF-LT), and fermented low-tannin (FM-LT). The results showed that fermentation increased glucose tolerance, increased red blood cell numbers and increased systolic blood pressure, but decreased flow-mediated vasodilation. Taken together, the overall effect of fermentation appears to be beneficial and improved FB nutritional value. Most interesting, even though the HP diet was grain-free, the diet did contain added taurine, and no adverse effects on cardiac function were observed, while glucose tolerance was impaired compared to NP-fed dogs. In summary, this study did not find evidence of adverse cardiac effects of pulses in ‘grain-free’ diets, at least not in the relatively resistant beagle breed over a 28-day period. More importantly, fermentation with C. utilis shows promise to enhance health benefits of pulses such as FB in dog food.

Effect of the Renin-Angiotensin-Aldosterone System Reactivity on Endothelial Function and Modulative Role of Valsartan in Male Subjects with Essential Hypertension

Background: The aim of the study was to evaluate the relationship between renin-angiotensin-aldosterone (RAA) system activity and reactivity, and the endothelial function profile in normotensive subjects (N), and in essential hypertensives (H), followed by analysis of the modulatory role of an angiotensin receptor blocker (ARB): valsartan, administered in the management of hypertension. Methods: A total of 101 male subjects were enrolled to the study: 31H and 70N. The nitric-oxide (NO) bioavailability (l-Arginine, asymmetric dimethylarginine (ADMA)), symmetric dimethylarginine (SDMA), endothelial vasodilative function (flow mediated dilation (FMD)), oxidative-stress markers (malonyldialdehyde (MDA), thiol index (GSH/GSSG), nitrotyrozine (N-Tyr)), and pro-inflammatory/angiogenic parameters (sICAM-1, sVCAM-1, PAI-1, sE-selectin, PAI-1, thromboxane -B2) were assessed at baseline, then after intravenous -l-arginine administration, which was repeated after the 4-day acetylsalicylic acid (ASA) administration (75 mg/24 h). In hypertensives, this whole protocol was repeated following 2 weeks of valsartan therapy. Results: No effect of valsartan and ASA on the flow-mediated vasodilation (FMD) and the NO bioavailability in hypertensives was observed. Administration of valsartan increased plasma renin activity (PRA), but without a decrease in the aldosterone levels. ASA treatment minimized the pre-existing differences between the groups, and increased the PRA in the N-subgroup with the highest ARR values. The blood concentrations of proinflammatory sICAM-1, sE-selectin, sVCAM-1, and PAI-1 were higher, whereas the anti-inflammatory 6-keto-PGF1 alpha level was lower in hypertensive subjects. The levels of angiogenic VEGF did not differ between groups. Conclusions: Our study does not confirm the modulative effect of valsartan on endothelial function. Normotensive men showed an increase in FMD after l-arginine administration, possibly indicating baseline impairment of the NO synthesis.

Endothelial Dysfunction, its Relationship with Chronic Periodontal Disease, and other Associated Risk Factors

Background: Chronic periodontitis is related to individual characteristics. However, it is precisely infectious in nature with the possibility of generating a chronic systemic inflammatory response that could favour its association with diseases, such as endothelial dysfunction, hypertension, CVD, and diabetes. Purpose: The aim of the study was to analyze the relationship of endothelial dysfunction measured by flow-mediated vasodilation in the brachial artery with periodontal disease and other possible factors. Methods: A case-control study was carried out in which those who had periodontitis were defined as cases, and those who were periodontally healthy or had gingivitis were defined as controls. A clinical history was obtained from all patients, and all patients underwent biofilm control and periodontal examinations. Blood tests were performed to determine CBC, glycaemia, total cholesterol, HDL-C, and LDL-C levels, and standardized procedures were used to measure flow-mediated dilation. Results: A total of 202 patients were included in this study: 101 controls [healthy/gingivitis] and 101 cases [periodontitis]. Regarding sex, glycaemia [p = 0.019] and triglycerides [p = 0.001] levels and initial flow-mediated vasodilation [p = 0.001] and final flow-mediated vasodilation [p = 0.001] values were higher in men, while HDL values ​​were lower [p = 0.001. The average age was higher for those in the group that presented dysfunction than for those in the group without dysfunction [p = 0.014]. When analyzing the percentage of patients with endothelial dysfunction in each of the groups, there were very few positive results obtained [5 per group]. Conclusion: Initial and final arterial vasodilation was lower in women than in men. Likewise, there were more cases of endothelial dysfunction in women. In this study, patients with endothelial dysfunction were older. Periodontitis was not associated with endothelial dysfunction.

Effects of Arm-cranking Training with Electrical Muscle Stimulation on Vessel Function

This study aimed to determine whether arm-cranking training with electrical muscle stimulation (EMS) results in a greater improvement in vessel function than performing the same exercise without EMS. First, nine healthy young men performed two 20-min arm-cranking trials at 50% V˙O2max with and without EMS applied to the lower limbs. The flow-mediated vasodilation (FMD) of the right brachial artery was measured using a high-resolution ultrasound device. Both FMD and normalized FMD were increased significantly after the arm-cranking with EMS trial, and significant differences were observed between the two trials. Second, 16 healthy adult men were randomly assigned to either the arm-cranking exercise training (A) group or arm-cranking training with EMS (A+EMS) group. The subjects were engaged in 20 min of arm-cranking at 50% V˙O2max twice a week for 8 weeks with/without EMS applied to the lower limbs. The FMD increased significantly after A+EMS training session and the FMD in A+EMS group was significantly higher than that in the A group. These results indicate that acute/chronic endurance arm-cranking with EMS applied to the lower limbs improves the brachial artery endothelial function more markedly than the same exercise without EMS.

Activating P2Y1 receptors improves function in arteries with repressed autophagy

Rationale: Shear-stress -induced nitric oxide (NO) generation by human arterial endothelial cells (HAECs) is prevented by pharmacological or genetic autophagy disruption. The response is restored by activating purinergic 2Y1 receptor (P2Y1-R) signaling to endothelial cell (EC) NO synthase (eNOS). Here we determined the translational relevance of these findings. Objective: Test the hypotheses that : (i) older humans and mice display blunted autophagy initiation and EC NO generation evoked by functional hyperemia; and that impaired intraluminal flow-mediated vasodilation displayed by : (ii) older mice with repressed EC autophagy; (iii) adult mice with pharmacological autophagy inhibition; and (iv) adult mice with EC specific autophagy-related gene 3 (Atg3) depletion, is rejuvenated by activating P2Y1-Rs. Methods and results: Rhythmic handgrip exercise elevated radial artery shear rate similarly in adult and older males. Compared to baseline, autophagy initiation, p-eNOSS1177 activation, and NO generation, occurred in radial artery ECs from adult but not older subjects. Relative to adult (7-month) mice, older (24-month) animals exhibited : (i) repressed EC mRNA and arterial protein indexes of autophagy and p-eNOSS1177 at baseline; (ii) blunted activation of EC autophagy and p-eNOSS1177 in response to treadmill-running; and (iii) impaired flow mediated arterial vasodilation examined ex vivo. Age-associated reductions in vasodilatory capacity were recapitulated in arteries from adult mice by : (i) NOS inhibition; (ii) autophagy impairment using 3-methyladenine (3-MA); (iii) EC Atg3 depletion (iecAtg3KO mice); (iv) P2Y1-R blockade; and (v) germline depletion of P2Y1-Rs. P2Y1-R activation using 2-methylthio-ADP (2-Me-ADP) restored shear-induced p-eNOSS1177 and NO generation in HAECs that was otherwise attenuated by: (i) 3-MA; or (ii) Atg3 knockdown. Importantly, 2-Me-ADP improved intraluminal flow-mediated vasodilation in arteries from : (i) adult mice treated with 3-MA; (ii) adult iecAtg3KO mice; and (iii) older animals. Conclusions: Arterial dysfunction concurrent with repressed EC autophagy is improved by activating P2Y1-Rs.

Comparison of Resveratrol Supplementation and Energy Restriction Effects on Sympathetic Nervous System Activity and Vascular Reactivity: A Randomized Clinical Trial

Background: Chronic sympathetic nervous system activation is associated with endothelial dysfunction and cardiometabolic disease, which may be modulated by resveratrol (RSV) and energy restriction (ER). This study aimed to examine the effects of RSV and ER on plasma noradrenaline (NA), flow-mediated vasodilation (ed-FMD), and endothelium-independent nitrate-mediated vasodilation (ei-NMD). Methods: The study included 48 healthy adults randomized to 30-days intervention of RSV or ER. Results: Waist circumference, total cholesterol, HDL-c, LDL-c, apoA-I, and plasma NA decreased in the ER group, whilst RSV increased apoB and total cholesterol, without changing plasma NA. No effects on vascular reactivity were observed in both groups. Plasma NA change was positively correlated with total cholesterol (r = 0.443; p = 0.002), triglycerides (r = 0.438; p = 0.002), apoA-I (r = 0.467; p = 0.001), apoB (r = 0.318; p = 0.032) changes, and ei-NMD (OR = 1.294; 95%CI: 1.021–1.640). Conclusions: RSV does not improve cardiometabolic risk factors, sympathetic activity, and endothelial function. ER decreases plasma NA and waist circumference as well as improves blood lipids, but does not modify endothelial function. Finally, plasma NA was associated with ei-NMD, which could be attributed to a higher response to nitrate in patients with greater resting sympathetic vasoconstriction.