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-beta-oxidation-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 (1-7 days) and dose-dependent (100-900 mg/kg every 12 h) manner. After 7 days of treatment with 2-OHOA (600 mg/kg), the systolic BP of SHRs was similar to that of normotensive Wistar Kyoto rats, returning to its initial hypertensive level after withdrawal of 2-OHOA. This treatment strongly increased the protein expression of the catalytic and regulatory RIalpha and RIIalpha PKA subunits as well as PKA activity in aortas from SHRs. Consistently, administration of the PKA inhibitor 8-bromo adenosine-3',5'-cyclic monophosphorothioate, Rp isomer, to 2-OHOA-treated SHRs induced a pronounced reversal (up to 59%) of the antihypertensive effect of 2-OHOA. Additionally, 2-OHOA completely reversed the pathological overexpression of aortic Rho kinase found in SHRs, suppressing the vasoconstrictory Rho kinase pathway.
Highlights
Olive oil consumption leads to high monounsaturated fatty acid intake, especially oleic acid, and has been associated with a reduced risk of hypertension
We examined for the first time whether the MUFA 2-hydroxyoleic acid (2-OHOA), a synthetic derivative of oleic acid with a hydroxyl group on the a-carbon that avoids its rapid degradation through the b-oxidation pathway [25], exhibits antihypertensive properties in the adult spontaneously hypertensive rats (SHRs), an animal model with established hypertension, compared with its normotensive counterpart, the Wistar Kyoto (WKY) rat, and whether the potential mechanisms mediating its antihypertensive action involve protein kinase A (PKA) and Rho kinase
After treatment of SHRs for 7 days, 2-OHOA reduced systolic blood pressure (BP) (254 mm Hg, 6 4%) (Fig. 1A), diastolic BP (251 mm Hg, 6 3%), and mean BP (252 mm Hg, 228 6 3%) (Fig. 1B) to values close to those measured in normotensive WKY rats
Summary
Olive oil consumption leads to high monounsaturated fatty acid intake, especially oleic acid, and has been associated with a reduced risk of hypertension. 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. During agonist-induced contraction of vascular smooth muscle cells, phosphorylation of myosin light chain (MLC) is a crucial step for force development [11] In this process, the extent of MLC phosphorylation depends on the equilibrium between the activity of Ca21-calmodulin-dependent MLC kinase and the MLC phosphatase.
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