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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.

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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)

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BACKGROUND AND PURPOSE: Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1. EXPERIMENTAL APPROACH: SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O(2) (•-) ) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively. KEY RESULTS: I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ET(B) mRNA expression, and down-regulated ET(A) mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ET(B) receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ET(B) receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ET(B) receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, N(ω) -nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O(2) (•-) production by increasing NADPH oxidase 1 (NOX-1) and p(47phox) mRNA. CONCLUSIONS AND IMPLICATIONS: Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ET(B) receptors and decrease in NO bioavailability.

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