Antihypertensive action of 2-hydroxyoleic acid in SHRs via modulation of the protein kinase A pathway and Rho kinase

Abstract

Olive oil consumption leads to high monounsaturated fatty acid intake, especially oleic acid, and has been associated with a reduced risk of hypertension. However, the molecular mechanisms and contribution of its different components to lower blood pressure (BP) require further evaluation. Here, we examined whether a synthetic, non-boxidation-metabolizable derivative of oleic acid, 2-hydroxyoleic acid (2-OHOA), can normalize BP in adult spontaneously hypertensive rats (SHRs) and whether its antihypertensive action involves cAMP-dependent protein kinase A (PKA) and Rho kinase, two major regulators of vascular smooth muscle contraction. Oral administration of 2-OHOA to SHRs induced sustained systolic BP decreases in a time-dependent

Oleic acid content is responsible for the reduction in blood pressure induced by olive oil

“…Indeed, this hypotensive effect can be reversed in rats by administration of the PKA blocker Rp-8-BrcAMP, which affects the last protein in this canonical signaling cassette (19). Together, these results indicate a direct relationship between the composition and structure of lipid membranes and BP regulation, which is supported by the relationships we have shown here.…”

“…cyclase-cAMP/PKA that provokes a lowering of the BP and limits the effects of other vasoconstriction pathways (18,19). Accordingly, deficient AC activity in vascular cells, caused by altered G protein levels and function, diminishes intracellular cAMP levels, a hallmark of hypertension in humans (38,39) and in experimental animal models (30).…”

“…High intake of the nonlamellar prone fatty acid, OA (and structurally related analogues or precursors, such as 2-hydroxyoleic acid, VOO, and TO), increases the concentration of cis-MUFA in membranes. This concentration regulates the localization, activity, and expression of important signaling molecules in the adrenergic receptor pathway, enhancing the production of vasodilatory stimuli (e.g., cAMP and PKA) and restricting vasoconstriction pathways (inositol-triphosphate, Ca 2ϩ , diacylglycerol, and Rho kinase) (19).…”

“…At the molecular level, OA and VOO regulate G protein-associated signaling both in vivo (in humans) and in cell culture (1,17). Interestingly, the hypotensive effect of 2-hydroxyoleic acid involves changes in the same signaling pathways as those affected by OA (18,19). However, some studies associate the cardioprotective activity of VOO with minor components characteristic of olive oil, such as ␣-tocopherol, polyphenols, and other phenolic compounds (16,(20)(21)(22)(23).…”

Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

“…In this context, we have recently demonstrated that an enhancement of the cAMP/PKA pathway in vascular tissue is responsible for the reduction of blood pressure observed in spontaneously hypertensive and normotensive SpragueDawley rats after 2-OHOA treatment. 11,33 In contrast, expression of COX8H and phosphorylation of CREB in rats treated with oleic acid declined to less than half of the levels of vehicle-treated control rats. This suggests that the high efficiency of 2-OHOA in the reduction of body weight is not caused by a simple potentiation of the activity of oleic acid but by a completely distinct mechanism.…”