Abstract

Recent evidence suggests that the reason Extra Virgin Olive Oil (EVOO) lowers blood pressure and reduces the risk of developing hypertension is partly due to minor components of EVOO, such as phenols. However, little is still known about the mechanism(s) through which EVOO phenols mediate anti-hypertensive effects. The aim of the present study was to investigate the mechanisms of action of EVOO phenols on mesenteric resistance arteries. A pressure myograph was used to test the effect of EVOO phenols on isolated mesenteric arteries in the presence of specific inhibitors of: (1) BKca channels (Paxillin, 10−5 M); (2) L-type calcium channels (Verapamil, 10−5 M); (3) Ryanodine receptor, RyR (Ryanodine, 10−5 M); (4) inositol 1,4,5-triphosphate receptor, IP3R, (2-Aminoethyl diphenylborinate, 2-APB, 3 × 10−3 M); (5) phospholipase C, PLC, (U73122, 10−5 M), and (6) GPCR-Gαi signaling, (Pertussis Toxin, 10−5 M). EVOO phenols induced vasodilation of mesenteric arteries in a dose-dependent manner, and this effect was reduced by pre-incubation with Paxillin, Verapamil, Ryanodine, 2-APB, U73122, and Pertussis Toxin. Our data suggest that EVOO phenol-mediated vasodilation requires activation of BKca channels potentially through a local increase of subcellular calcium microdomains, a pivotal mechanism on the base of artery vasodilation. These findings provide novel mechanistic insights for understanding the vasodilatory properties of EVOO phenols on resistance arteries.

Highlights

  • We demonstrated that Extra Virgin Olive Oil (EVOO)-phenol-induced vasodilation is endotheliumindependent and occurs through activation of the large-conductance calcium-activated potassium (BKca ) channels in the vascular smooth muscle cells (VSMCs), but does not involve signaling pathways mediated by nitric oxide (NO)−, prostanoids, or the cyclic nucleotides cAMP and cGMP [20]

  • We tested the effect of EVOO phenols (0.1–10 μM) on mesenteric artery (MA) pre-constricted with phenylephrine

  • Our study shows that phenols dilate resistance in a dose-dependent on mesenteric artery in the absence and in the presence of the specific inhibitor of themanGPCR

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Summary

Introduction

Systemic arterial hypertension is the most common preventable risk factor for cardiovascular disease (CVD) [1] and is a leading cause of morbidity, disability, and mortality in the world, with an estimated 17.92 million deaths in 2015 [2]. It is well-established that healthy lifestyle choices, such as diet, exercise, and abstinence from smoking, are associated with a lower risk of CVD [3,4]. Epidemiological and clinical studies indicate that daily intake of at least two tablespoons of EVOO can lower blood pressure, thereby decreasing the risk of developing

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