Effects of ranolazine on vasomotor responses of rat aortic rings.

BACKGROUND AND AIMS: Ranolazine is a piperazine derivative that was approved in 2006 for the treatment of chronic stable angina. Compared with first-line drugs currently used to treat angina, beneficial effects of ranolazine occur without changing hemodynamic parameters such as heart rate and blood pressure. In the present study the effects of ranolazine on vasomotor responses of rat aortic rings were examined. METHODS: Pharmacological evaluation was performed by analyzing the vasomotor responses of ranolazine on aortic rings of adult male Wistar rats precontracted with phenylephrine (10(-5) M). In each experiment we used a pair of rings (with and without endothelium) from the same aorta and superfused in the same bath. RESULTS: Ranolazine (10(-6)-10(-4) M) induced a concentration-dependent relaxation of phenylephrine-precontracted rings. The relaxation was only partially dependent on the presence of the endothelium (56.78 ± 6.81% in rings with endothelium and 47.88 ± 4.70% in rings without endothelium). In rings with endothelium, L-NAME induced a shift to the right of the concentration-response curve to ranolazine. Blocking the cyclooxygenase pathway induced a leftward shift of the concentration relaxation curve to ranolazine in both types of rings and increased the ranolazine-induced relaxation in rings without endothelium. CONCLUSIONS: Ranolazine has a vasodilatory effect that is predominantly endothelium-independent. The synthesis/release of nitric oxide by the endothelium may, however, contribute to its relaxing action. These effects of ranolazine may contribute to its beneficial effects in patients with stable angina.

Protective effect of Arthrospira maxima on fatty acid composition in fatty liver.

BACKGROUND: Arthrospira maxima has been widely used for nutritional purposes. Additionally, A. maxima has shown immunomodulator, antiviral, antioxidant, vasomotor and hypolipidemic effects in laboratory and animal studies. A. maxima prevents fatty liver induced by either carbon tetrachloride (CCl4) or fructose-rich diet; however, the liver lipid composition in these models is not clearly known yet. The aim of this study was to evaluate the effects of A. maxima on the liver lipid profile in CCl4-induced steatohepatitis. METHODS: A single sublethal, intraperitoneal dose of CCl4 was administered to male Wistar rats fed a diet with or without 5% A. maxima. Liver lipids: total lipids, triacylglycerols, total cholesterol, free fatty acids, and thiobarbituric acid reactive substances were assessed 24 and 48 h after injury with CCl4. Additionally, triacylglycerols, total cholesterol and aspartate aminotransferase were evaluated in blood. RESULTS: Forty eight hours after CCl4 treatment, rats fed a diet without A. maxima had serum aspartate aminotransferase and liver triacylglycerols values that were, respectively, 2.2 and 1.4 times higher than those of animals receiving 5% A. maxima in their diet. The same pattern was observed for liver free fatty acids and thiobarbituric acid reactive substances. The groups fed a diet with A. maxima and treated with CCl4 showed a higher saturated fatty acid liver content than the groups without A. maxima in their diet. The percentage of unsaturated fatty acids increased 48 h after CCl4 treatment, but its value was 0.5 times lower in the group receiving A. maxima than in the group fed without A. maxima. In the liver, all animals receiving A. maxima showed a trend towards a lower percentage of unsaturated fatty acids, despite the mentioned increase 48 h after CCl4 treatment. CONCLUSIONS: The results suggest that, in the fatty liver induced by CCl4, the hepatoprotective effect of A. maxima involves (a) an antioxidant mechanism and (b) a lower unsaturation of the liver fatty acids. The preventive effect of A. maxima on the liver lipid changes induced by CCl4 could be partially explained by its antioxidant action and the ability to increase the synthesis/release of nitric oxide, but not by its soluble dietary fiber.

Ethanolic extract of Spirulina maxima alters the vasomotor reactivity of aortic rings from obese rats.

BACKGROUND: Aortic rings with endothelium excised from fructose-fed obese rats develop more tension in response to phenylephrine and relax less in response to carbachol than corresponding rings from lean rats. This altered vascular reactivity is prevented when Spirulina maxima is added to the fructose-rich diet. In the present study the effects of a raw ethanolic extract of Spirulina maxima on the vasomotor responses of aorta rings from sucrose-fed obese hypertensive rats were analyzed. METHODS: The experiments were performed on aorta rings from sucrose-fed obese male rats. For each experiment, a pair of rings from the same aorta (one with intact endothelium, the other without a functional endothelium) was used. In this study we analyzed, in vitro, the effects of the ethanolic extract of Spirulina maxima on the reactivity of the aortic rings to phenylephrine and to carbachol. RESULTS: On rings with endothelium, the extract produced the following effects: a) a concentration-dependent (0.06-1.0 mg/mL) decrease of the contractile response to phenylephrine; b) a rightward shift and a decrease in maximal developed tension, of the concentration-response curve to phenylephrine; c) a concentration-dependent relaxation of phenylephrine-precontracted rings. These effects persisted in the presence of indomethacin but were prevented by L-NAME. The extract had no effect on the concentration-response curve of phenylephrine-precontracted rings to carbachol. On endothelium-denuded rings the extract caused a significant rightward shift of the concentration response curve to phenylephrine without any effect on maximal tension development. CONCLUSIONS: These results suggest that, in rings from obese rats, the extract, in addition to increasing the synthesis/release of NO, also inhibits the synthesis/release of a cyclooxygenase-dependent vasoconstrictor metabolite of arachidonic acid, which is increased in obesity.