RESUMEN
Diabetes was induced in rats by administration of a single i.p. injection of streptozotocin (50 mg/kg body wt). After 7 d, diabetic rats were further treated with insulin or 1,25-dihydroxycholecalciferol [1,25(OH)2D3] for an additional 5-7 d. Control, diabetic, diabetic + insulin, and diabetic + 1,25(OH)2D3 rats were then killed, their proximal small intestines were removed, and villus-tip epithelial cells were isolated and used to prepare brush-border membrane vesicles. Preparations from each of these groups were then analyzed and compared with respect to their amiloride-sensitive, electroneutral Na(+)-H+ exchange activity, using 22Na uptake as well as acridine orange techniques. The results of these experiments demonstrated that (a) H+ gradient-dependent 22Na uptake as well as Na+ gradient-dependent transmembrane H+ fluxes were significantly increased in diabetic vesicles compared to their control counterparts, (b) kinetic studies demonstrated that this enhanced 22Na uptake in diabetes was a result of increased maximal velocity (Vmax) of this exchanger with no change in apparent affinity (Km) for Na+, (c) serum levels of 1,25(OH)2D3 were significantly lower in diabetic animals compared with their control counterparts; and (d) insulin or 1,25(OH)2D3 treatment restored the Vmax alterations to control values, without any significant changes in Km, concomitant with significantly increasing the serum levels of 1,25(OH)2D3 in diabetic animals. These results indicate that Na(+)-H+ activity is significantly increased in proximal small intestinal luminal membranes of streptozotocin-induced diabetic rats. Moreover, alterations in the serum levels of 1,25(OH)2D3 may, at least in part, explain this enhanced antiporter activity and its correction by insulin.
Asunto(s)
Calcitriol/farmacología , Diabetes Mellitus Experimental/metabolismo , Insulina/farmacología , Intestino Delgado/metabolismo , Sodio/metabolismo , Animales , Intestino Delgado/ultraestructura , Cinética , Masculino , Microvellosidades/metabolismo , Potasio/metabolismo , Protones , RatasRESUMEN
The enhancement of prostacyclin (PGI2) formation in the cardiac and renal vessel wall by nafazatrom (BAY g 6575) and the vascular effects of this drug were studied in a series of experiments on perfused isolated rat hearts and kidneys. A dose-dependent increase of prostacyclin release (measured as 6-Keto-PGF1 alpha levels, delta % of control) from the vascular endothelium was achieved when nafazatrom was applied in concentrations ranging from 5 X 10(-7) to 10(-5) g/ml. In the heart, the minimal effective dose of nafazatrom was 5 X 10(-7) g/ml causing a 23 delta % increase of PGI2 release; maximal stimulation of PGI2 was 276 delta % at 5 X 10(-6) g/ml nafazatrom. In the kidney, only at the highest concentration of 10(-5) g/ml an increase of PGI2 to 192 delta % was found. Concomitant to the PGI2 release, in both organs, a reduction of perfusion pressure (delta % of control) was observed. Minimal vasodilation in the heart was - 9.6 delta % (5 X 10(-6) g/ml nafazatrom); the maximal effect was - 25.7 delta % (5 X 10(-6) g/ml nafazatrom). In the kidney, the only observed reduction of perfusion pressure was - 12 delta % at 10(-5) g/ml nafazatrom. The cyclooxygenase inhibitor indomethacin (10(-5) g/ml) blocked vasodilation produced by nafazatrom (5 X 10(-6) g/ml); delta P % was 0.5 + 1.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Epoprostenol/metabolismo , Fibrinolíticos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Pirazoles/farmacología , Pirazolonas , Arteria Renal/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Técnicas In Vitro , Masculino , Músculo Liso Vascular/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Diabetes was induced in male Lewis rats by a single injection of streptozocin (50 mg/kg body wt ip). After 10-14 days, diabetic and age- and sex-matched control animals were killed, and their proximal small intestines were removed. Villus-tip, mid-villus, and lower-villus enterocytes were harvested from each group with a method that combined divalent cation chelation with mild mechanical dissociation. These fractions were used as starting material to prepare brush-border membrane vesicles. Preparations from each of these fractions were then analyzed and compared with respect to their Na(+)-gradient-dependent and Na(+)-independent D-glucose transport, lipid fluidity, and lipid composition. The results of these experiments demonstrated that 1) maximum rates of Na(+)-gradient-dependent D-glucose transport (Vmax) were greatest in membrane vesicles prepared from mature cells (villus tip and mid villus) of control rats; 2) the glucose concentration producing half-maximal rates of transport (Km), however, was significantly lower in lower-villus membrane vesicles of control rats, suggesting that a distinct glucose transporter existed in the membranes of these relatively immature enterocytes; 3) Na(+)-gradient-dependent, but not Na(+)-independent, D-glucose uptake was greater in diabetic membrane vesicles prepared from mid-villus and lower-villus fractions but not in vesicles prepared from villus-tip cells; and 4) no obvious relationship between alterations in membrane lipid fluidity and enhanced uptake of Na(+)-gradient-dependent D-glucose by these transporter(s) could be established in this experimental model of acute diabetes mellitus.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Glucosa/metabolismo , Intestino Delgado/metabolismo , Fluidez de la Membrana , Microvellosidades/metabolismo , Animales , Transporte Biológico Activo , División Celular , Replicación del ADN , Intestino Delgado/citología , Intestino Delgado/patología , Cinética , Masculino , Músculo Liso/citología , Músculo Liso/metabolismo , Músculo Liso/patología , Ratas , Ratas Endogámicas Lew , Valores de ReferenciaRESUMEN
In 38 patients with chronic obstructive lung disease (COLD), lung function tests, blood gas analysis, catheterisation examination of the right heart, and long-term (Holter) ECG were performed. In comparison with normal subjects, all the patients had a higher mean 24-hour heart rate of 97 +/- 11/minute, and a disturbance of the physiological day/night rhythmicity. Seventeen patients (group I) revealed no major arrhythmias (Lown I to III). More than 50 per cent of the patients (group II) were found to have complex arrhythmias (Lown IV), together with an elevated incidence of polymorphic ventricular and superventricular extrasystoles. A significant correlation of the arrhythmias with the severity of the obstruction or pulmonary hypertension was not observed. Only the long-term follow-up of these patients will provide us with information about the prognostic significance of the complex arrhythmias and about indications for anti-arrhythmic treatment.