Effect of melatonin on vascular responses in aortic rings of aging rats.

In old animals a marked reduction in endothelium-dependent relaxation occurs. Since there is evidence that the endothelial dysfunction associated with aging may be partly related to the local formation of reactive oxygen species, the purpose of this study was to examine the effect of the natural antioxidant melatonin (10(-5)mol/l) on in vitro contractility of aged aortic rings under conditions of increased oxidative stress (40 m mol/l glucose concentration in medium). Experiments were carried out in 18-20 months old, Wistar male rats, using adult (6-7 months old) animals as controls. A higher plasma lipid peroxidation was found in aged rats as compared to the younger ones. In a first experiment, dose-response curves for acetylcholine-induced relaxation of aortic rings were conducted. Analyzed as a main factor in a factorial ANOVA, age decreased and melatonin augmented the relaxing response to acetylcholine. melatonin's restoring effect on aortic ring relaxation was found in aged aortic rings only and was more pronounced in the presence of a high glucose medium. In a second experiment, the effect of melatonin on the contractility response to phenylephrine of intact or endothelium-denuded aortic rings obtained from aged or control rats was examined in normal or high glucose medium. A main factor analysis in the factorial ANOVA indicated that age and operation augmented, and melatonin decreased, aortic ring contractility response to phenylephrine. Melatonin's restoring effect on aortic contractility was seen in aged aortic rings. The effect of age or a high glucose medium on phenylephrine-induced contractility was more pronounced in the absence of an intact endothelium. Aging did not affect the relaxant response of intact or endothelium-denuded rings to sodium nitroprusside. The results support the improvement by melatonin of vascular response in aging rats, presumably via its antioxidant activity.

Melatonin restores endothelium-dependent relaxation in aortic rings of pancreatectomized rats.

In rats turned hyperglycemic by a subtotal pancreatectomy, a decreased relaxation response of aortic rings to acetylcholine (ACh) was found; this effect was amplified by preincubation in a high glucose medium (44 mmol/L). The relaxation response to ACh did not occur in endothelium-denuded rings or after the aortic rings were exposed to l-nitro-arginine methyl ester [L-NAME, a nitric oxide (NO) synthase inhibitor]. Incubation with the NO donor sodium nitroprusside (SNP) restored the impaired relaxation response seen in endothelium-denuded or L-NAME-treated aortic rings. Pancreatectomy decreased the vasorelaxation of aortic rings caused by SNP. Only in pancreatectomized rats, incubation in a high glucose medium impaired the relaxation effect of SNP. To assess whether melatonin preincubation reversed the impaired relaxation response to ACh (intact endothelium aortic rings) or to SNP (endothelium-denuded or L-NAME-treated rings) in hyperglycemic rats, cumulative dose-response curves were performed in the presence of 10(-5) mol/L melatonin. Melatonin preincubation did not modify ACh-induced relaxation of aortic rings in a normal glucose concentration but was highly effective in preventing the impairment of relaxation caused by a high glucose solution. Melatonin was also effective in restoring the impaired SNP-induced vasorelaxation seen in endothelium-denuded or L-NAME-treated aortic rings from hyperglycemic rats. The results further support the improvement by melatonin of the endothelial-mediated relaxation in blood vessels of diabetic rats.

Effect of melatonin on vascular reactivity in pancreatectomized rats.

The present study was undertaken to assess whether the improvement of contractile performance of aortic rings by melatonin described in streptozotocin diabetic rats also occurs in another model of type I diabetes, the pancreatectomized rats. Adult male Wistar rats submitted to a subtotal pancreatectomy and exhibiting altered levels of fasting glucose and an abnormal tolerance glucose test, were used. Sham-operated laparotomized rats were employed as controls. Dose-response curves for acetylcholine-induced, endothelium-related relaxation of aortic rings (after previous exposure to phenylephrine) and for phenylephrine-induced vasoconstriction were conducted. This protocol was repeated with rings pre-incubated in a high glucose solution (44 mmol/l). Pancreatectomy decreased significantly acetylcholine-induced relaxation of aortic rings, but not phenylephrine-induced vasoconstriction, the effect being amplified by preincubation in high glucose solution. The deleterious effect of a high glucose medium was more pronounced in pancreatectomized rats. Melatonin (10(-5) M) did not modify acetylcholine-induced relaxation in normal glucose concentration but was effective to prevent the impairment of relaxation brought about by exposure to high glucose solution. The contractile response to phenylephrine of aortic rings obtained from pancreatectomized rats was not affected by melatonin. The results further support the improvement by melatonin of endothelial-mediated relaxation in blood vessels of diabetic rats.

Positividade dos anticorpos antitiroidianos na doença de Graves / Positivity of antithyroid antiboidies in Graves' disease

Os auto-anticorpos descritos na doença de Graves säo imunoglobulinas pertencentes à classe IgG que dirigem-se especificamente a certos antígenos tiroidianos, destacando-se entre eles: tireoglobulina (antitireoglobulina), peroxidade tiroidiana (antimicrossomia/antiperoxidade) e receptor do hormônio tireotrófico (TRab). Com o objetivo de avaliar a prevalência dos auto-anticorpos na doença de Graves descompensada, estudamos 46 pacientes virgens de tratamento. Concordante com os dados da literatura, o anticorpo anti-receptor de TSH mostrou-se o melhor marcador da doença de Graves, com 92,4 por cento de positividade

Activación cardiocirculatoria en ratas anestesiadas con Ketamina: efectos de la premedicación con Diazepam / Cardiostimulatory activation in rats anesthetized with Ketamine: effects of premedication with Diazepam

La anestesia con ketamina (A-Kt) provoca un aumento de la presión arterial (PA) y de la frecuencia cardíaca (FC), por activación del sistema nervioso simpático. En este estudio se evalúo el efecto de la medicación con diazepam (DZ), flumazenil (FZ), picrotoxina (PTX), y PK11195, sobre la respuesta cardiovascular observada durante la A-Kt. Se emplearon ratas Wistar machos, divididas en 9 grupos (n=10): I- A-Kt; II- A-Kt y DZ; III- A-Kt e inyectado con FZ; IV- A-Kt, inyectado con FZ y DZ; V- A-Kt e inyectado con PTX, VI- A-Kt, inyectado con PTX y DZ; VII- A-Kt e inyectado con PK11195; VIII- A-Kt, DZ e inyectado con PK11195; IX- Controles despiertos. La A-Kt provocó en las ratas de los grupos I y IV un aumento de la PA y FC (P<0,01) y en el grupo VII (P<0,01); (IV-VII vs I P>0,05). En los animales del grupo II no se registró respuesta presora (P>0.05), pero aumentó la FC 45 min después de la inyección de Kt (P<0,05). En los grupos V y VI se incrementó la PA (P<0.01; V vs VI P>0,05), y la FC (P<0,01) respectivamente. La inyección de PK11195 no antagonizó la acción del DZ (grupo VIII) en los animales A-Kt. La ausencia de variaciones significativas en la PA en el grupo II, asociado al aumento observado en los grupos I, III, IV, V, VI, VII y VIII sugieren que receptores GABA A modularían la estimulación simpática cardiovascular evocada por la Kt. Posiblemente, tanto los efectos de diazepam como los de la Kt involucrarían a estructuras tromboencefálicas que intervienen en los mecanismos de regulación central de la actividad cardiocirculatoria.

Activación cardiocirculatoria en ratas anestesiadas con Ketamina: efectos de la premedicación con Diazepam / Cardiostimulatory activation in rats anesthetized with Ketamine: effects of premedication with Diazepam

La anestesia con ketamina (A-Kt) provoca un aumento de la presión arterial (PA) y de la frecuencia cardíaca (FC), por activación del sistema nervioso simpático. En este estudio se evalúo el efecto de la medicación con diazepam (DZ), flumazenil (FZ), picrotoxina (PTX), y PK11195, sobre la respuesta cardiovascular observada durante la A-Kt. Se emplearon ratas Wistar machos, divididas en 9 grupos (n=10): I- A-Kt; II- A-Kt y DZ; III- A-Kt e inyectado con FZ; IV- A-Kt, inyectado con FZ y DZ; V- A-Kt e inyectado con PTX, VI- A-Kt, inyectado con PTX y DZ; VII- A-Kt e inyectado con PK11195; VIII- A-Kt, DZ e inyectado con PK11195; IX- Controles despiertos. La A-Kt provocó en las ratas de los grupos I y IV un aumento de la PA y FC (P<0,01) y en el grupo VII (P<0,01); (IV-VII vs I P>0,05). En los animales del grupo II no se registró respuesta presora (P>0.05), pero aumentó la FC 45 min después de la inyección de Kt (P<0,05). En los grupos V y VI se incrementó la PA (P<0.01; V vs VI P>0,05), y la FC (P<0,01) respectivamente. La inyección de PK11195 no antagonizó la acción del DZ (grupo VIII) en los animales A-Kt. La ausencia de variaciones significativas en la PA en el grupo II, asociado al aumento observado en los grupos I, III, IV, V, VI, VII y VIII sugieren que receptores GABA A modularían la estimulación simpática cardiovascular evocada por la Kt. Posiblemente, tanto los efectos de diazepam como los de la Kt involucrarían a estructuras tromboencefálicas que intervienen en los mecanismos de regulación central de la actividad cardiocirculatoria. (AU)