Published online before print December 8, 2003, doi: 10.1161/01.HYP.0000107778.85528.b5
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(Hypertension. 2004;43:249.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
2-Hydroxyoleic Acid
A New Hypotensive Molecule
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.
Correspondence to Pablo V. Escribá, Laboratory of Molecular and Cellular Biomedicine, IUNICS, Department of Biology, Associate Unit of the Instituto de la Grasa (CSIC), University of the Balearic Islands, Ctra Valldemossa Km 7.5, E-07122 Palma de Mallorca, Spain. E-mail pablo.escriba{at}uib.es
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 G
s, 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 ß-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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