2-hydroxyoleic acid: a new hypotensive molecule.
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 Galpha(s), but not Galpha(i2) or Galpha(o), increased in membranes from the hearts and aortas of 2-OHOA-treated rats, whereas in heart membranes, the density of Galpha(q)/11 and protein kinase Calpha proteins was also augmented. These molecular alterations were reflected in the increase in cAMP levels after Galpha(s) protein and beta-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 Galpha(s) activation, which might be attributed to enhanced expression of Galpha(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.
Alemany
Regina
R
Laboratory of Molecular and Cellular Biomedicine, IUNICS, Department of Biology, Associate Unit of the Instituto de la Grasa, University of the Balearic Islands, Palma de Mallorca, Spain.
Terés
Silvia
S
Baamonde
Carmela
C
Benet
Mikhail
M
Vögler
Oliver
O
Escribá
Pablo V
PV
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
C483229:2-hydroxyoleic acid; D000959:Antihypertensive Agents; D009829:Oleic Acids; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases