Published Online
on December 8, 2003

A more recent version of this article appeared on February 1, 2004

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Submitted on September 22, 2003
Revised on October 15, 2003

2-Hydroxyoleic Acid. A New Hypotensive Molecule

Regina Alemany; Silvia Terés; Carmela Baamonde; Mikhail Benet; Oliver Vögler; and Pablo V. Escribá^*

From the Laboratory of Molecular and Cellular Biomedicine, IUNICS, Department of Biology, Associate Unit of the Instituto de la Grasa (CSIC), University of the Balearic Islands, Palma de Mallorca, Spain.

^* To whom correspondence should be addressed. E-mail: pablo.escriba{at}uib.es.

Abstract--Recent studies have shown that diets rich in monounsaturated fatty acids (MUFAs) from olive oil, a natural source of oleic acid, have beneficial effects on blood pressure (BP) in hypertensive patients. With this in mind, we investigated whether a synthetic derivative of the MUFA oleic acid, 2-hydroxyoleic acid (2-OHOA), was capable of regulating the BP of Sprague-Dawley rats. Intraperitoneal and oral administration of 2-OHOA to rats induced significant and sustained decreases in BP in a time-dependent manner. Without affecting heart rate, treatments for 7 days provoked reductions in systolic BP of 20 to 26 mm Hg. At the molecular level, the density of Gs, but not Gi₂ or Go, increased in membranes from the hearts and aortas of 2-OHOA-treated rats, whereas in heart membranes, the density of Gq/11 and protein kinase C proteins was also augmented. These molecular alterations were reflected in the increase in cAMP levels after Gs protein and -adrenergic receptor stimulation. On the contrary, inhibitory hormones reduced adenylyl cyclase activity to the same extent in 2-OHOA-treated rats as in vehicle-treated ones. Our results indicate that cardiovascular tissues from 2-OHOA-treated rats exhibited increased cAMP production in response to Gs activation, which might be attributed to enhanced expression of Gs proteins. As a result of this change, a significant reduction in systolic BP was observed. Therefore, BP can be lowered by administration of 2-OHOA, which might represent the first member of a new family of antihypertensive drugs.

Key words: blood pressure • fatty acids • signal transduction • G proteins • hypotension

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