Esperanza Herradón

Characterization of the vasorelaxant mechanisms of the endocannabinoid anandamide in rat aorta

Studies in isolated preparations of vascular tissue (mainly resistance vessels) provide evidence that anandamide exerts vasorelaxation. The aim of the present work was to further characterize the mechanisms involved in the vascular response induced by anandamide in a conduit vessel, rat aorta.

Cannabinoid/agonist WIN 55,212-2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS.

Diabetes increases cardiac damage after myocardial ischaemia. Cannabinoids can protect against myocardial ischaemia/reperfusion injury. The aim of this study was to examine the cardioprotective effect of the cannabinoid agonist WIN 55,212‐2 (WIN) against ischaemia/reperfusion injury in an experimental model of type 2 diabetes. We performed these experiments in the Zucker diabetic fatty rat, and focused on the role of cannabinoid receptors in modulation of cardiac inducible nitric oxide synthase (iNOS)/endothelial‐type nitric oxide synthase (eNOS) expression.

Cannabinoid-induced delayed gastric emptying is selectively increased upon intermittent administration in the rat: role of CB1 receptors

Background  Cannabinoids acutely administered depress central, cardiovascular and gastrointestinal functions. These effects might be modified upon repeated administration. Compared to the effects induced by daily administration, those induced by intermittent administration are less known. The effect of intermittent treatment with the CB1/CB2 cannabinoid agonist WIN55,212‐2 (WIN) was studied in the rat.

Vasorelaxation Caused by Cannabinoids: Mechanisms in Different Vascular Beds

Cannabinoids (natural, endogenous and synthetic compounds) produce vasorelaxation in resistance and conduit arteries. Several putative mechanisms have been proposed to explain this effect of cannabinoids. The aim of the present review is to discuss the different mechanisms involved in the vasorelaxant effect of endogenous and synthetic cannabinoids in resistance and conduit arteries. Research on the vascular effects of cannabinoids suggests that the magnitude of the vasorelaxation and the mechanisms involved are not identical in all vascular beds with one or two mechanisms predominating. Either extracellular or intracellular mechanisms are involved. With regard to the former, the stimulation of cannabinoid CB1, CB2 or nonCB1/nonCB2 cannabinoid receptors and the stimulation of vanilloid receptors, transient potential vanilloid receptors, on perivascular nerve endings with the subsequent release of the vasodilator neurotransmitter calcitonin gene-related peptide have been described. With regard to the latter, the main mechanisms implicated include nitric oxide release, metabolism to vasoactive arachidonic metabolites or prostanoid analogues, or endothelium derived hyperpolarising factor release. The knowledge of these mechanisms is crucial to identify new therapeutic targets and to understand the consequences in different vascular beds.

Vascular toxicity of chemotherapeutic agents.

Cancer chemotherapy is not free of undesirable side effects. With respect to the cardiovascular system, cardiotoxicity is a well-described and potentially lethal side effect of certain chemotherapeutic agents, such as anthracyclines. However, in the last few years, several clinical studies have taken into account the fact that some non-anthracycline chemotherapy treated-patients also have a significantly increased risk of cardiovascular events. The exact mechanism of this toxicity is not known, and several possibilities, including vascular autonomic neuropathy and vascular damage, have been proposed. The aim of the present review was to collate information on the clinical and experimental evidence regarding vascular toxicity for each of the different groups of chemotherapeutic agents. The mechanisms proposed to underlie this toxicity are also discussed.

Effects of chronic dietary exposure to monosodium glutamate on feeding behavior, adiposity, gastrointestinal motility, and cardiovascular function in healthy adult rats

Monosodium glutamate (MSG) is a flavor‐enhancer widely used as a food additive. However, its safe dietary concentration and its toxicity, including its possible implication in the recent metabolic syndrome pandemia, is still a controversial issue. Therefore, a deep knowledge of its effects upon regular dietary use is needed. Our aim was to evaluate the effects of chronic exposure to MSG on feeding behavior, abdominal fat, gastrointestinal motility, and cardiovascular function in rats.

Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.