2-Hydroxyoleic Acid

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 Gαs, but not Gαi 2 or Gαo, increased in membranes from the hearts and aortas of 2-OHOA–treated rats, whereas in heart membranes, the density of Gαq/11 and protein kinase Cα proteins was also augmented. These molecular alterations were reflected in the increase in cAMP levels after Gαs protein and β-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 Gαs activation, which might be attributed to enhanced expression of Gαs 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.