2-Hydroxyoleic Acid

Abstract

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 G␣s, but not G␣i 2 or G␣o, increased in membranes from the hearts and aortas of 2-OHOA-treated rats, whereas in heart membranes, the density of G␣q/11 and protein kinase C␣ proteins was also augmented. These molecular alterations were reflected in the increase in cAMP levels after G␣s 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 G␣s activation, which might be attributed to enhanced expression of G␣s 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 Ⅲ fatty acids Ⅲ signal transduction Ⅲ G proteins Ⅲ hypotension M any alterations in the structure and function of the cell membrane have been associated with hypertension. Changes in the plasma or membrane lipid composition have been reported in both hypertensive humans 1 and in animal models of hypertension. 2,3 These changes have been associated with abnormalities in cation transport systems, 4 cytosolic Ca 2ϩ regulation, 5 and impaired signal transduction. 6 As a result, it has been proposed that modifications of the membrane lipid composition can affect the physical and functional properties of membranes and in consequence, might account for the alterations in signaling implicated in the physiological control of blood pressure (BP). In this context, long-term fatty acid (FA) intake is known to influence both membrane lipid composition and BP. Olive oil, a natural source of the monounsaturated FA (MUFA) oleic acid, has been shown to have beneficial effects on BP (when high doses are consumed for long periods) and is associated with a low incidence of coronary heart disease. 7 Olive oil consumption causes favorable changes in plasma lipid and lipoprotein profiles 8,9 and also in the phospholipid content and FA composition of both erythrocyte membranes from hypertensive patients and aorta membranes from spontaneously hypertensive rats. 10,11 Moreover, a slight reduction in saturated fat intake along with the use of olive oil markedly lowers the ...

Oleic acid content is responsible for the reduction in blood pressure induced by olive oil

“…Sprague-Dowley rats were used because they constitute a valuable model with little variability, appropriate to study the regulatory effects of fatty acids on BP (18). On the other hand, SHR is a well known model of hypertension (19), used in the present work to determine whether VOO might be useful to control high BP in human hypertensive subjects.…”

“…Solid lines represent the regression of the correlations, whose correlation coefficients (r) and statistical significance (P) are shown in both cases. chronic treatments as described (18). The polyclonal antisera against G␣i3 and G␣q/11 were obtained from Santa Cruz Biotecnology and that against G␣i2 was from PerkinElmer, and the anti-PLC␤1 antiserum was from BD Biosciences/ Transduction Laboratories.…”

“…cyclase-cAMP/PKA that provokes a lowering of the BP and limits the effects of other vasoconstriction pathways (18,19). Accordingly, deficient AC activity in vascular cells, caused by altered G protein levels and function, diminishes intracellular cAMP levels, a hallmark of hypertension in humans (38,39) and in experimental animal models (30).…”

“…At the molecular level, OA and VOO regulate G protein-associated signaling both in vivo (in humans) and in cell culture (1,17). Interestingly, the hypotensive effect of 2-hydroxyoleic acid involves changes in the same signaling pathways as those affected by OA (18,19). However, some studies associate the cardioprotective activity of VOO with minor components characteristic of olive oil, such as ␣-tocopherol, polyphenols, and other phenolic compounds (16,(20)(21)(22)(23).…”

Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

“…In this context, we have recently demonstrated that an enhancement of the cAMP/PKA pathway in vascular tissue is responsible for the reduction of blood pressure observed in spontaneously hypertensive and normotensive SpragueDawley rats after 2-OHOA treatment. 11,33 In contrast, expression of COX8H and phosphorylation of CREB in rats treated with oleic acid declined to less than half of the levels of vehicle-treated control rats. This suggests that the high efficiency of 2-OHOA in the reduction of body weight is not caused by a simple potentiation of the activity of oleic acid but by a completely distinct mechanism.…”