Acute Effects of Intravenous Administration of Polyunsaturated Fatty Acids on Blood Pressure and Heart Rate in U46619- and Noradrenaline-infused Rats
Daisuke Chino
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Satsuki Yuda
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Yukiko Suzuki
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Fumi Hatsuyama
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Kyosuke Sato
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Keisuke Obara
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Yoshio Tanaka *
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
*Author to whom correspondence should be addressed.
Abstract
Experimental studies and epidemiological surveys have indicated that chronic oral administration of the n-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic (DHA) or eicosapentaenoic (EPA) acids reduces blood pressure in hypertensive patients. However, few reports have described the acute blood pressure lowering effects of these PUFAs. In this study, we determined the acute effects of DHA and EPA on blood pressure of rats with increased blood pressure resulting from continuous injection of pressor substances. U46619 (a TXA2 receptor agonist) and noradrenaline (NA) were continuously infused (500 μg/kg/h each) into urethane-anesthetized male Wistar rats and produced sustained elevated mean blood pressure (MBP). In both U46619- and NA-infused rats, bolus administration of DHA (3–30 mg/kg, i.v.) reduced blood pressure in a dose-dependent manner, although the MBP reduction was greater in U46619-infused rats. Similarly, administration of EPA (3–30 mg/kg, i.v.) also induced a greater reduction in MBP of U46619-infused rats. In contrast, bolus administration of linoleic acid (3–30 mg/kg, i.v.), an n-3 type unsaturated fatty acid, failed to reduce blood pressure in all drug-infused rats. Finally, administration of the nitric oxide donor sodium nitroprusside (0.3–100 μg/kg, i.v.) showed a similar blood pressure drop in all drug-infused rats. These findings clearly indicate that both DHA and EPA induce acute blood pressure reduction in anesthetized rats, and suggest that the blood pressure drop is mediated via the TXA2 receptor. These characteristic blood pressure lowering effects of these PUFAs are likely to be useful for prevention and treatment of hypertension.
Keywords: Docosahexaenoic acid, eicosapentaenoic acid, linoleic acid, TXA2 receptor, acute blood pressure changes, polyunsaturated fatty acids