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-G_αi 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.

Accumulating evidence has shown the beneficial health effects of extra virgin olive oil (EVOO) consumption in reducing blood pressure and preventing the risk of developing hypertension. Some studies associate the hypotensive activity of EVOO to a minor component—the phenols. This study was designed to investigate the effects of EVOO phenols on the rat resistance mesenteric artery (MA) and to find out the possible vascular pathways involved. The experiments were carried out using a pressurized myograph, which allowed the effects of phenols on isolated MA to be tested under different conditions: (a) with endothelium removed; (b) with inhibition of nitric oxide synthase by N_ω-Nitro-l-arginine methyl ester hydrochloride (l-NAME, 10⁻⁴ M) + N_ω-Nitro-l-arginine (l-NNA, 10⁻⁴ M); (c) with inhibition of cyclooxygenase by indomethacin (10⁻⁵ M); (d) with inhibition of guanylate cyclase by 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ,10⁻⁵ M) or adenylate cyclase by 9-(Tetrahydro-2′-furyl)adenine (SQ, 10⁻⁵ M); (e) with depolarization by high potassium chloride (40 mM); and (f) with inhibition of the large conductance Ca²⁺–potassium channels (BK_Ca2+) with paxilline (10⁻⁵ M). EVOO phenols induce vasodilation of the endothelium, mediated by a direct effect on smooth muscle cells (SMC) by activation of BK_Ca2+ channels, an action by which phenols can regulate the vascular tone of the resistance artery. Phenols can be regarded as bioactive molecules that may contribute to the antihypertensive effects of EVOO.

Although the clinical differences between hemodialysis (HD) and peritoneal dialysis (PD) are well established, the specific biological mechanisms underlying these differences remain incompletely understood. We performed untargeted proteomic and transcriptomic analyses of peripheral blood mononuclear cells (PBMCs) from healthy controls (CTRs) and patients with chronic kidney disease undergoing HD or PD. Key findings were validated in an independent cohort using standardized biomolecular techniques. Bioinformatic analysis identified 36 differentially expressed proteins and 19 transcripts between HD and PD according to the predefined FDR-adjusted significance threshold. Functional enrichment analysis revealed that these factors were primarily involved in cellular senescence, aging, and stress-response pathways. Among the identified molecules, interferon regulatory factor 8 (IRF8) was the only factor consistently upregulated in HD compared with PD in both omics analyses. This finding was confirmed by ELISA in an independent cohort (p < 0.0001). Kinase enrichment analysis prioritized Checkpoint Kinase 2 (CHEK2), which was also identified by proteomics, as a predicted upstream regulator and warrants further investigation. Overall, these findings identify distinct molecular signatures in PBMCs from HD and PD patients and suggest a potential association between HD and increased PBMC IRF8 abundance and a senescence-related signature, which requires validation in larger and longitudinal cohorts.