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Papers In Press, published online ahead of print May 10, 2006
J. Lipid Res., doi:10.1194/jlr.M500520-JLR200
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Submitted on November 30, 2005
Revised on April 4, 2006
Accepted on May 9, 2006

Antihypertensive action of 2-hydroxyoleic acid in SHR mediated by enhancement of the protein kinase A pathway and downregulation of Rho-kinase

Regina Alemany, Oliver Vogler, Silvia Teres, Carolina Egea, Carmela Baamonde, Francisca Barcelo, Carlos Delgado, Karl H. Jakobs, and Pablo V. Escriba

Department of Biology, University of the Balearic Islands, Palma de Mallorca, Baleares E-07122

Corresponding Author: regina.alemany{at}uib.es

Olive oil consumption leads to high monounsatured fatty acid intake, especially oleic acid, and has been associated with 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 (SHR) and whether its antihypertensive action involves cAMP-activated protein kinase (PKA) and Rho-kinase, two major regulators of vascular smooth muscle contraction. Oral administration of 2-OHOA to SHR induced sustained systolic BP decreases in a time (1-7 days)- and dose (100-900 mg/kg every 12 h)-dependent manner. After 7 days treatment with 2-OHOA (600 mg/kg), systolic BP of SHR 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 SHR. Consistently, administration of the PKA inhibitor, Rp-8-Br-cAMP, to 2-OHOA-treated SHR 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 SHR, suppressing the vasoconstrictory Rho-kinase pathway.


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 Am. J. Physiol. Heart Circ. Physiol.Home page
G. H. Borchert, M. Giggey, F. Kolar, T. M. Wong, P. H. Backx, and P. V. Escriba
2-Hydroxyoleic acid affects cardiomyocyte [Ca2+]i transient and contractility in a region-dependent manner
Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1948 - H1955.
[Abstract] [Full Text] [PDF]


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