Un ensayo sobre la libertad : "el poder" de Bertrand de Jouvenel

Fil: Camilión, Oscar H. Universidad de Buenos Aires. Facultad de Derecho. Cátedra de Derecho Político. Buenos Aires, Argentin

Notas acerca de las teorías del "contrato social"

Fil: Camilión, Oscar H. Universidad de Buenos Aires. Facultad de Derecho. Derecho Político. Buenos Aires, Argentin

Regression of hypertensive myocardial fibrosis by Na+/H+ exchange inhibition

We have recently reported that the inhibition of the Na+/H+ exchanger (NHE) during 1 month in spontaneously hypertensive rats (SHR) is followed by regression of cardiomyocyte hypertrophy but not of myocardial fibrosis. The aim of this study was to evaluate whether a treatment of longer duration could reduce myocardial fibrosis and stiffness. SHR received 3.0 mg/kg per day of the specific NHE-1 inhibitor cariporide; the effect on cardiomyocyte cross-sectional area, myocardial collagen volume fraction, collagen synthesis, and myocardial stiffness (length-tension relation in left papillary muscles) was evaluated at several time points (after 1, 2, or 3 months). A slight decrease of ≈5 mm Hg in systolic blood pressure was observed after 1 month of treatment with no further changes. After 2 and 3 months of treatment, the size of cardiomyocytes remained within normal values and myocardial fibrosis progressively decreased to normal level. Accordingly, myocardial stiffness and the serum levels of the carboxyterminal propeptide of procollagen type I, a marker of collagen type I synthesis, were normalized after 3 months. Left ventricular weight decreased from 910±43 (in untreated SHR) to 781±21 mg (treated SHR) after 3 months of treatment. No difference in body weight between treated and untreated SHR was observed after this period of treatment. The present data allow us to conclude that in the SHR the administration of an NHE-1 inhibitor for 2 or 3 months leads to the normalization of collagen type I synthesis, myocardial collagen volume fraction, and stiffness.Facultad de Ciencias MédicasFacultad de Ciencias Veterinaria

Regression of hypertensive myocardial fibrosis by Na+/H+ exchange inhibition

We have recently reported that the inhibition of the Na+/H+ exchanger (NHE) during 1 month in spontaneously hypertensive rats (SHR) is followed by regression of cardiomyocyte hypertrophy but not of myocardial fibrosis. The aim of this study was to evaluate whether a treatment of longer duration could reduce myocardial fibrosis and stiffness. SHR received 3.0 mg/kg per day of the specific NHE-1 inhibitor cariporide; the effect on cardiomyocyte cross-sectional area, myocardial collagen volume fraction, collagen synthesis, and myocardial stiffness (length-tension relation in left papillary muscles) was evaluated at several time points (after 1, 2, or 3 months). A slight decrease of ≈5 mm Hg in systolic blood pressure was observed after 1 month of treatment with no further changes. After 2 and 3 months of treatment, the size of cardiomyocytes remained within normal values and myocardial fibrosis progressively decreased to normal level. Accordingly, myocardial stiffness and the serum levels of the carboxyterminal propeptide of procollagen type I, a marker of collagen type I synthesis, were normalized after 3 months. Left ventricular weight decreased from 910±43 (in untreated SHR) to 781±21 mg (treated SHR) after 3 months of treatment. No difference in body weight between treated and untreated SHR was observed after this period of treatment. The present data allow us to conclude that in the SHR the administration of an NHE-1 inhibitor for 2 or 3 months leads to the normalization of collagen type I synthesis, myocardial collagen volume fraction, and stiffness.Facultad de Ciencias MédicasFacultad de Ciencias Veterinaria

Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na+/H+ exchanger

Objective: Experiments were performed to examine the effect of chronic inhibition of the Na+/H+ exchanger isoform-1 (NHE-1) on cardiac hypertrophy of spontaneously hypertensive rats (SHR). Methods: SHR were orally treated during 1 month with two different doses (0.3 and 3.0 mg/kg/day) of the NHE-1 inhibitor, cariporide, or nifedipine (10.0 mg/kg/day). Results: The two doses of cariporide did not differ in their effects after 1 month of treatment, since both induced a slight decrease in systolic blood pressure (SBP) of ∼6 mmHg and regression of the heart weight to body weight ratio (mg/g) from 3.28±0.05 to 3.04±0.05 (0.3 mg) and 2.99±0.10 (3.0 mg, P<0.05). Nifedipine, given for the same period, produced similar reduction in the hypertrophy index (3.03±0.05), but with a much greater decrease in arterial pressure (35.6±7.4 mmHg). Chronic treatment with cariporide induced a complete regression of the augmented cross sectional area of left ventricular myocytes without significant changes in collagen content, serum procollagen 1 propeptide levels or myocardial distensibility. Conclusions: NHE inhibition represents a novel approach to induce regression of pathological hypertrophy of the heart. The finding can be rationalized mechanistically by previous in vitro studies suggesting a role of the NHE in the development of myocardial hypertrophy.Facultad de Ciencias MédicasFacultad de Ciencias VeterinariasCentro de Investigaciones Cardiovasculare

Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na+/H+ exchanger

Objective: Experiments were performed to examine the effect of chronic inhibition of the Na+/H+ exchanger isoform-1 (NHE-1) on cardiac hypertrophy of spontaneously hypertensive rats (SHR). Methods: SHR were orally treated during 1 month with two different doses (0.3 and 3.0 mg/kg/day) of the NHE-1 inhibitor, cariporide, or nifedipine (10.0 mg/kg/day). Results: The two doses of cariporide did not differ in their effects after 1 month of treatment, since both induced a slight decrease in systolic blood pressure (SBP) of ∼6 mmHg and regression of the heart weight to body weight ratio (mg/g) from 3.28±0.05 to 3.04±0.05 (0.3 mg) and 2.99±0.10 (3.0 mg, P<0.05). Nifedipine, given for the same period, produced similar reduction in the hypertrophy index (3.03±0.05), but with a much greater decrease in arterial pressure (35.6±7.4 mmHg). Chronic treatment with cariporide induced a complete regression of the augmented cross sectional area of left ventricular myocytes without significant changes in collagen content, serum procollagen 1 propeptide levels or myocardial distensibility. Conclusions: NHE inhibition represents a novel approach to induce regression of pathological hypertrophy of the heart. The finding can be rationalized mechanistically by previous in vitro studies suggesting a role of the NHE in the development of myocardial hypertrophy.Facultad de Ciencias MédicasFacultad de Ciencias VeterinariasCentro de Investigaciones Cardiovasculare

Bay K 8644 enhances the outflow of [³H]-noradrenaline and [³H]-DOPEG from isolated rat atria

The effect of Bay K 8644 (a dihydropyridine Ca²⁺-channel activator), was examined on spontaneous and stimulus-evoked release of tritium from isolated rat atria prelabelled with [³H]-noradrenaline. Bay K8644 (3μmol/l) significantly increased atrial rate from 206±7 to 259±9 beats·min⁻¹ (P<0.05) and also tritium outflow (expressed as fractional rate of loss in min⁻¹ × 10³) from 6.49±0.35 to 8.61±0.74 (P<0.05). Neither the maximal rate nor the overflow of tritium induced by stimulation of sympathetic nerve terminals was changed by the compound. The increase in basal tritium outflow produced by Bay K 8644 was calcium-dependent. However, it could not be antagonized by nitrendipine. The overflow of tritium induced by Bay K 8644 consisted mainly of 3,4-dihydroxyphenylglycol ([³H]-DOPEG), indicating that the compound produces a leakage from the storage vesicles of sympathetic nerve terminals of the isolated rat atria.Centro de Investigaciones Cardiovasculare

Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na+/H+ exchanger

Objective: Experiments were performed to examine the effect of chronic inhibition of the Na+/H+ exchanger isoform-1 (NHE-1) on cardiac hypertrophy of spontaneously hypertensive rats (SHR). Methods: SHR were orally treated during 1 month with two different doses (0.3 and 3.0 mg/kg/day) of the NHE-1 inhibitor, cariporide, or nifedipine (10.0 mg/kg/day). Results: The two doses of cariporide did not differ in their effects after 1 month of treatment, since both induced a slight decrease in systolic blood pressure (SBP) of ∼6 mmHg and regression of the heart weight to body weight ratio (mg/g) from 3.28±0.05 to 3.04±0.05 (0.3 mg) and 2.99±0.10 (3.0 mg, P<0.05). Nifedipine, given for the same period, produced similar reduction in the hypertrophy index (3.03±0.05), but with a much greater decrease in arterial pressure (35.6±7.4 mmHg). Chronic treatment with cariporide induced a complete regression of the augmented cross sectional area of left ventricular myocytes without significant changes in collagen content, serum procollagen 1 propeptide levels or myocardial distensibility. Conclusions: NHE inhibition represents a novel approach to induce regression of pathological hypertrophy of the heart. The finding can be rationalized mechanistically by previous in vitro studies suggesting a role of the NHE in the development of myocardial hypertrophy.Facultad de Ciencias MédicasFacultad de Ciencias VeterinariasCentro de Investigaciones Cardiovasculare

Regression of hypertensive myocardial fibrosis by Na+/H+ exchange inhibition

We have recently reported that the inhibition of the Na+/H+ exchanger (NHE) during 1 month in spontaneously hypertensive rats (SHR) is followed by regression of cardiomyocyte hypertrophy but not of myocardial fibrosis. The aim of this study was to evaluate whether a treatment of longer duration could reduce myocardial fibrosis and stiffness. SHR received 3.0 mg/kg per day of the specific NHE-1 inhibitor cariporide; the effect on cardiomyocyte cross-sectional area, myocardial collagen volume fraction, collagen synthesis, and myocardial stiffness (length-tension relation in left papillary muscles) was evaluated at several time points (after 1, 2, or 3 months). A slight decrease of ≈5 mm Hg in systolic blood pressure was observed after 1 month of treatment with no further changes. After 2 and 3 months of treatment, the size of cardiomyocytes remained within normal values and myocardial fibrosis progressively decreased to normal level. Accordingly, myocardial stiffness and the serum levels of the carboxyterminal propeptide of procollagen type I, a marker of collagen type I synthesis, were normalized after 3 months. Left ventricular weight decreased from 910±43 (in untreated SHR) to 781±21 mg (treated SHR) after 3 months of treatment. No difference in body weight between treated and untreated SHR was observed after this period of treatment. The present data allow us to conclude that in the SHR the administration of an NHE-1 inhibitor for 2 or 3 months leads to the normalization of collagen type I synthesis, myocardial collagen volume fraction, and stiffness.Facultad de Ciencias MédicasFacultad de Ciencias Veterinaria

Positive chronotropic effect of Bay K 8644: participation of endogenous norepinephrine

The chronotropic effect of Bay K 8644, a dihydropyridine known to increase the slow inward current, was studied in spontaneously beating rat atria. Increases in atrial rate were concentration-dependent and the maximal increase (106 ± 10 beats/min) was obtained at 3 × 10⁻⁶ mol/l. Reserpine pretreatment, or propranolol 3 × 10⁻⁷ mol/l, or propranolol plus prazosin 10⁻⁶ mol/l decreased the maximum chronotropic effect of Bay K 8644 by about 60%. Blockade of the removal mechanisms of catecholamines (hydrocortisone 3 × 10⁻⁵ mol/l plus cocaine 10⁻⁵ mol/1) did not prevent the chronotropic effect of the compound. Exposure to Bay K 8644 increased the spontaneous outflow of tritium from atria preloaded with [3H]-norepinephrine by 30%. The results indicate that Bay K 8644 produces positive chronotropic effects through two mechanisms: a direct one and an indirect mechanism that involves the participation of norepinephrine released from sympathetic nerve endings.Centro de Investigaciones Cardiovasculare