Characterization of hypotensive and vasorelaxant effects of PHAR-DBH-Me a new cannabinoid receptor agonist.

The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings precontracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018-185 µg/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 µg/kg. A concentration-dependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10-6 M), the addition of PHAR-DBH-Me to the superfusion solution (10-12-10-5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB1 receptor antagonist (AM 251) did not modify the response, while CB2 receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10-5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB2 receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.

Effects of Oleamide on the Vasomotor Responses in the Rat.

Introduction: Cardiovascular effects of endocannabinoids (eCBs) have generated considerable interest since it has been suggested that the eCB system could become the new pharmacological target, either by blocking its activity or by promoting its effects on several cardiovascular diseases such as hypovolemic and septic shock or hypertension. The purpose of this study was to examine the effects of oleamide on several vasomotor responses in adult rats. Materials and Methods: Blood pressure (BP) was measured both directly and indirectly. Coronary flow was quantified with Langendorf preparation, and the vasomotor responses induced by oleamide were analyzed in the aortic rings. Results: Oleamide induced a decrease in BP, by both direct and indirect methods, which were dose dependent. An increase in coronary flow was observed with Langendorf preparation depending on the dose. Oleamide produced a vasodilator response in aortic rings pre-contracted with phenylephrine (10-5 M), which was concentration and endothelium dependent. This relaxing effect was of minor magnitude than that induced with the same dose on BP. L-NAME did not modify these effects. However, indomethacin induced a shift to the left of the concentration-response curve to oleamide and an increase in the magnitude of maximum vasodilation in rings with endothelium. Oleamide produced the maximal relaxant response at 10-5 M concentration. Conclusions: Oleamide has both in vivo and in vitro vasodilator effects. Vasodilator effects could be mediated by compounds synthesized/released by the endothelium (hyperpolarizing factor) or acting directly on vascular smooth muscle in aortic rings. The TRPV1 and CB1R receptors could mediate these effects. Finally, the results suggest that oleamide probably induces the synthesis/release of a vasoconstrictor prostanoid.

Subchronic stress effects on vascular reactivity in C57BL/6 strain mice.

BACKGROUND AND AIMS: There is a close relationship between psychosocial stress and the development of cardiovascular diseases. It has been reported that there are different alterations in endothelial function in this relationship. However, results obtained in different experimental stress models are controversial. Herein, we studied the effects of subchronic stress induced by movement restraint on several cardiovascular responses and plasma corticosterone concentration in male adult mice. METHODS: Experiments were performed in adult male mice of C57BL/6 strain. Animals were allocated into three groups: Control group A, without manipulation; Control group B, with manipulation (quantitation of blood pressure); and Experimental group, with quantitation of blood pressure and exposure to movement restraint. In vivo, heart rate and blood pressure were registered. In vitro, in aortic rings, vascular reactivity was analyzed. Additionally, plasma corticosterone concentration was quantified. RESULTS: In vivo, subchronic stress did not produce changes on heart rate either on blood pressure. In vitro, aortic rings with and without endothelium from control group B and experimental group showed: 1) a significant decrease in the maximal tension developed in response to phenylephrine; 2) this decrease was reverted by L-NAME. However, aortic rings from all groups, developed the same tension in response to high K+ solution. In aortic rings from animals of the experimental group, an increase in the maximal relaxation induced by carbachol was observed. This relaxation was prevented and/or reversed by L-NAME. Plasma corticosterone concentration was higher in the experimental group than that in the control group A. CONCLUSIONS: Exposition to subchronic movement restraint did not produce alterations in neurovegetative responses in this strain mice. But according to vasomotor responses observed, the results suggest that this subchronic stress model induces an increase in the synthesis/release of nitric oxide, both from endothelial cells and vascular smooth muscle. In accordance with the aforementioned results, we propose that C57BL/6 mice strain is sensitive to subchronic movement restraint stress model.

Protective effect of Spirulina platensis on fatty liver induced by a single sublethal dose of carbon tetrachloride in wistar rats / Efecto protector de la Spirulina platensis sobre el hígado graso inducido con tetracloruro de carbono, a una dosis subletal, en ratas Wistar

It has been reported that Spirulina maxima and other natural products are effective in attenuating hepatic damage. In this study were analyzed the effects of five days dietary Spirulina platensis (5 percent) in rats with fatty liver induced by CCl4 (2 mL/kg b.w.). Animals were sacrificed at 24 and 48 h post-treatment. In the liver were evaluated total lipids by gravimetry and lipid profile by enzymatic-colorimetric methods, the concentration of thiobarbituric acid reactive substances and nitric oxide by chemical methods. In serum, alanine aminotransferase (kinetic method) and lipid profile were evaluated. The most important effects on the liver were: attenuation in lipid peroxidation, minimal variations on the total fatty acid methyl esters profile, and nitric oxide. These results suggest that Spirulina platensis could be used for fatty liver treatment as an alimentary supplement.

Se ha reportado que la Spirulina maxima y otros productos naturales son efectivos para atenuar el daño hepático. El objetivo del presente estudio fue evaluar los efectos de la Spirulina platensis dietaria (5 por ciento) durante cinco días en ratas con hígado graso inducido por CCl4 (2 mL/kg p.c.). Los animales fueron sacrificados a las 24 y 48 h postratamiento. En el hígado se evaluaron los lípidos totales por gravimetría y el perfil de lípidos por métodos enzimático-colorimétricos, la concentración de sustancias reactivas al ácido tiobarbitúrico y óxido nítrico por métodos químicos. En suero fueron evaluados alanina aminotransferasa (método cinético) y perfil de lípidos. Los principales efectos sobre el hígado fueron: la atenuación de la lipoperoxidación, variaciones mínimas en el perfil de metil ésteres de ácidos grasos totales y del óxido nítrico. Estos resultados sugieren que la Spirulina platensis podría ser utilizada como suplemento alimenticio en el tratamiento de hígado graso.