Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats.

BACKGROUND AND PURPOSE: We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. EXPERIMENTAL APPROACH: Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. KEY RESULTS: Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. CONCLUSIONS AND IMPLICATIONS: The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats.

El ejercicio aeróbico moderado evita la disfunción endotelial y neuronal producida por una dieta rica en grasas en arteria mesentérica de rata / Aerobic exercise training avoids endothelial and neuronal dysfunction produced by a high fat diet in rat mesenteric artery

Objetivo: Determinar si la obesidad inducida por una dieta rica en grasa (HFD) está asociada con modificaciones en las funciones endotelial o neuronal, y los efectos del entrenamiento aeróbico moderado en estos cambios. Materiales y métodos: : Se utilizaron: (i) ratas control (dieta estándar); (ii) ratas alimentadas con una dieta HFD durante ocho semanas, y (iii) ratas HFD sometidas a un entrenamiento aeróbico moderado. Se analizaron las respuestas vasomotoras a acetilcolina (ACh) y estimulación eléctrica (EE), el efecto de L-NAME sobre dichas respuestas, la respuesta vasodilatadora al donante de óxido nítrico (NO) DEA-NO, las liberaciones de NO y de O2.- y la expresión de nNOS y eNOS. Resultados: La ingesta de la dieta HFD disminuyó la respuesta vasodilatadora a ACh e incrementó la respuesta vasoconstrictora a EE. El efecto del L-NAME fue menor en ambos casos en ratas HFD. Las liberaciones de NO endotelial y neuronal fueron disminuidas en ratas HFD. La liberación de O2.- solo aumentó en arterias de ratas HFD con endotelio. La vasodilatación a DEA-NO disminuyó sólo en arterias HFD con endotelio. HFD no modificó la expresión de eNOS, pero disminuyó la expresión de nNOS. Todos estos cambios fueron evitados por el entrenamiento aeróbico moderado. Conclusión: La práctica de ejercicio aeróbico moderado evitó la disfunción de la inervación nitrérgica perivascular y endotelial inducidas por una dieta HFD, evitando el desarrollo de mecanismos que favorecen la hipertensión (AU)

Objective: We investigated whether high-fat diet (HFD)-induced obesity was associated with modifications on endothelial or innervation functions, and the possible effects of aerobic exercise training on these changes. Methods: (i) Control rats (standard diet); (ii) rats fed a HFD for 8 weeks; and (iii) HFD rats submitted to an aerobic exercise training were used. Vasomotor responses to acetylcholine (ACh) and electric field stimulation (EFS), the effect of L-NAME in these responses, vasomotor responses to nitric oxide (NO) donor DEA-NO, NO and O2.- releases, and nNOS and eNOS expression were analysed. Results: : HFD decreased ACh vasodilatation and increased EFS-induced contraction. The effect of L-NAME was lower in both cases in HFD segments. Both endothelial and neuronal NO releases were decreased in HFD. O2.- release was augmented only in endothelium-intact HFD arteries. DEA-NO was decreased only in endothelium- intact segments from HFD. HFD decreased nNOS and did not modify eNOS expressions. All the modifications described were avoided after training. Conclusion: Aerobic exercise training avoided endothelial and nitrergic innervation dysfunction induced by a HFD, thus avoiding the development of mechanisms which lead to hypertension (AU)

Factors involved in rosuvastatin induction of insulin sensitization in rats fed a high fat diet.

BACKGROUND AND AIM: To investigate whether rosuvastatin can improve insulin sensitivity in overweight rats having a high fat diet (HFD). The potential mechanisms involved in this action were evaluated, including SIRT-1, other factors involved in glucose metabolism and stress signaling pathways. METHODS AND RESULTS: Male Wistar rats (n = 30) were divided into three groups: (i) rats fed a standard diet (3.5% fat); (ii) rats fed a HFD (33.5% fat); and (iii) rats fed a HFD and treated with rosuvastatin (15 mg/kg/day). Evolution: 7 weeks. HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Plasma levels of cholesterol, triglycerides, VLDL, glucose and insulin and leptin/adiponectin ratio were higher in HFD rats, and rosuvastatin treatment reduced them. SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 protein levels in white adipose tissue (WAT) were lower, and JNK was higher in HFD rats compared to controls. Rosuvastatin treatment normalized expression of these mediators. Endothelium-dependent relaxation was reduced in mesenteric rings from HFD rats compared to controls and rosuvastatin enhanced it in HFD rats. CONCLUSION: Rosuvastatin treatment reduced insulin resistance without affecting body weight or WAT loss in HFD rats. Reduction of leptin and JNK, and enhancement of SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 expression in WAT could contribute to insulin sensitization. Normalization of SIRT-1 expression in WAT could be considered a key novel mechanism that aids in explaining the beneficial effects of rosuvastatin on the amelioration of glucose metabolism and the arrangement of multiple signaling pathways participating in insulin resistance in overweight HFD rats.

Relevance of vascular peroxisome proliferator-activated receptor γ coactivator-1α to molecular alterations in atherosclerosis.

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is emerging as a novel factor that plays a critical role in integrating signalling pathways in the control of cellular and systemic metabolism. We investigated the role of vascular expression of PGC-1α and related factors, such as sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ (PPARγ) and adiponectin, during the atherosclerotic process. Endothelial function, vascular superoxide anion production and inflammatory mediators were also evaluated. This study was carried out in male New Zealand rabbits fed a diet containing 0.5% cholesterol and 14% coconut oil for 8 weeks. Animals developed mixed dyslipidaemia and atherosclerotic lesions, which were associated with endothelial dysfunction, aortic overproduction of superoxide anions and inflammation. Expression of PGC-1α, SIRT1, PPARγ and adiponectin was reduced (P<0.05) in aorta from atherosclerotic rabbits. Levels of PGC-1α were correlated negatively (P<0.05) with total cholesterol levels, aortic superoxide anion production and tumour necrosis factor-α expression, and positively (P<0.05) with maximal relaxation in response to acetylcholine. The observed results suggest that PGC-1α could be considered to be a link between the main atherosclerotic processes (endothelial dysfunction, oxidation and inflammation) and alterations of other factors involved in vascular wall integrity, such as SIRT1, PPARγ and adiponectin.

Endothelium modulates vasoconstrictor response to prostaglandin I2 in rat mesenteric resistance arteries: interaction between EP1 and TP receptors.

BACKGROUND AND PURPOSE: Prostacyclin (PGI(2)) is usually described as an endothelium-derived vasodilator, but it can also induce vasoconstriction. We studied the vasomotor responses to PGI(2) in resistance arteries and the role of thromboxane (TP) and prostaglandin E(2) (EP) receptors in this effect. EXPERIMENTAL APPROACH: Mesenteric resistance arteries were obtained from Sprague-Dawley rats. Vasomotion to PGI(2) was studied in segments of these arteries with and without endothelium and in presence of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the potassium channel blockers apamin plus charybdotoxin, the non-selective EP receptor antagonist AH6809, the selective TP receptor antagonist SQ29548 or the EP(1) receptor antagonist SC19220. PGI(2)-induced NO release was analysed in the absence or presence of SQ29548, AH6809 or SC19220. KEY RESULTS: PGI(2) caused contractions in arterial segments that were increased by endothelium removal, L-NAME or L-NAME plus apamin plus charybdotoxin and abolished by SQ29548. In segments with endothelium, AH6809 or SC19220 almost abolished the contractions to PGI(2); this effect was prevented by L-NAME, L-NAME plus apamin plus charybdotoxin or by endothelium removal. PGI(2) induced NO release that was inhibited by the prostacyclin receptor (IP receptor) antagonist, RO1138452, and increased by SQ29548, SC19220 and AH6809. The increase in NO release induced by these separate drugs was inhibited by RO1138452. CONCLUSIONS AND IMPLICATIONS: PGI(2) activated the TP receptor in mesenteric resistance arteries and produced vasoconstriction, which the endothelium modulated through TP and EP(1) receptors. PGI(2) also released endothelium-derived hyperpolarizing factor and, through IP receptor activation, induced NO release, which in turn, was antagonized by TP and EP(1) receptor activation.

Chronic ouabain treatment increases the contribution of nitric oxide to endothelium-dependent relaxation.

The aim of this study was to analyze the contribution of nitric oxide, prostacyclin and endothelium-dependent hyperpolarizing factor to endothelium-dependent vasodilation induced by acetylcholine in rat aorta from control and ouabain-induced hypertensive rats. Preincubation with the nitric oxide synthase inhibitor N-omega-nitro-L-arginine methyl esther (L-NAME) inhibited the vasodilator response to acetylcholine in segments from both groups but to a greater extent in segments from ouabain-treated rats. Basal and acetylcholine-induced nitric oxide release were higher in segments from ouabain-treated rats. Preincubation with the prostacyclin synthesis inhibitor tranylcypromine or with the cyclooxygenase inhibitor indomethacin inhibited the vasodilator response to acetylcholine in aortic segments from both groups. The Ca2+-dependent potassium channel blocker charybdotoxin inhibited the vasodilator response to acetylcholine only in segments from control rats. These results indicate that hypertension induced by chronic ouabain treatment is accompanied by increased endothelial nitric oxide participation and impaired endothelium-dependent hyperpolarizing factor contribution in acetylcholine-induced relaxation. These effects might explain the lack of effect of ouabain treatment on acetylcholine responses in rat aorta.

Chronic ouabain treatment increases the contribution of nitric oxide to endotheliumdependent relaxation

The aim of this study was to analyze the contribution of nitric oxide, prostacyclinand endothelium-dependent hyperpolarizing factor to endothelium-dependentvasodilation induced by acetylcholine in rat aorta from control and ouabain-inducedhypertensive rats. Preincubation with the nitric oxide synthase inhibitor N-omeganitro-L-arginine methyl esther (L-NAME) inhibited the vasodilator response toacetylcholine in segments from both groups but to a greater extent in segments fromouabain-treated rats. Basal and acetylcholine-induced nitric oxide release were higherin segments from ouabain-treated rats. Preincubation with the prostacyclin synthesisinhibitor tranylcypromine or with the cyclooxygenase inhibitor indomethacininhibited the vasodilator response to acetylcholine in aortic segments from bothgroups. The Ca2+-dependent potassium channel blocker charybdotoxin inhibited thevasodilator response to acetylcholine only in segments from control rats. Theseresults indicate that hypertension induced by chronic ouabain treatment is accompaniedby increased endothelial nitric oxide participation and impaired endotheliumdependenthyperpolarizing factor contribution in acetylcholine-induced relaxation.These effects might explain the lack of effect of ouabain treatment on acetylcholineresponses in rat aorta (AU)

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Orchidectomy increases beta-adrenoceptor activation-mediated neuronal nitric oxide and noradrenaline release in rat mesenteric artery.

BACKGROUND/AIMS: A previous study has demonstrated that endogenous male sex hormones do not alter neuronal nitric oxide (NO) release in rat mesenteric artery. However, the regulatory role of endogenous male sex hormones on noradrenaline (NA) release in rat mesenteric artery is not known. The present study was designed to analyze whether endogenous male sex hormones influence the NA release induced by electrical field stimulation (EFS), as well as the possible modification in NA and neuronal NO release by presynaptic beta-adrenoceptor activation. METHODS: For this purpose, mesenteric arteries from control and orchidectomized male Sprague-Dawley rats were used. Basal and EFS-induced neuronal NO and NA release, as well as the contractile effect induced by EFS, was measured. RESULTS: Basal and EFS-induced neuronal NO and NA release were similar in arteries from control and orchidectomized rats. The beta-adrenoceptor agonist clenbuterol did not modify EFS-induced neuronal NO and NA release in arteries from control rats. In contrast, in arteries from orchidectomized animals, clenbuterol increased both neuronal NO and NA release; this increase was prevented by incubation with the beta-adrenoceptor antagonist propranolol. However, the contractile response elicited by EFS was not modified by clenbuterol in either group of rats. CONCLUSIONS: These results show that orchidectomy does not alter the EFS-induced NA release. What is more, activation of presynaptic beta-adrenoceptors does not modify EFS-induced NA and neuronal NO release in arteries from control rats although it increases the release of both neurotransmitters in arteries from orchidectomized rats. Despite these modifications, the EFS-induced contractile response is preserved in arteries from orchidectomized rats.

Aspectos biologicos de las rickettsias. I. Clasificacion. Morfologia y composicion quimica (revision). / Biological aspects of rickttsiae. I.Classification. Morphology and chemical composition (review)

Se hace, en el presente trabajo, una breve revision de los aspectos fundamentales de la clasificacion, la morfologia y la composicion quimica de las rickettsias de interes medico. La clasificacion se realiza atendiendo a los grupos clasicos basados fundamentalmente en la patologia. En cuanto a la morfologia, se exponen distintos metodos de coloracion usados en microscopia optica para las rickettsias, asi como los detalles encontrados en estos microorganismos mediante microscopia electronica.Se hace referencia, finalmente, a los componentes quimicos rickettsiales, con alusion especial a aquellos que pueden tener funcion antigenica