RESUMEN
GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron diseases. Homozygous gle1(-/-) mutant zebrafish display various aspects of LCCS, showing severe developmental abnormalities including motor neuron arborization defects and embryonic lethality. A previous gene expression study on spinal cord from LCCS fetuses indicated that oligodendrocyte dysfunction may be an important factor in LCCS. We therefore set out to investigate the development of myelinating glia in gle1(-/-) mutant zebrafish embryos. While expression of myelin basic protein (mbp) in hindbrain oligodendrocytes appeared relatively normal, our studies revealed a prominent defect in Schwann cell precursor proliferation and differentiation in the posterior lateral line nerve. Other genes mutated in LCCS have important roles in Schwann cell development, thereby suggesting that Schwann cell deficits may be a common factor in LCCS pathogenesis. These findings illustrate the potential importance of glial cells such as myelinating Schwann cells in motor neuron diseases linked to RNA processing defects.
Asunto(s)
Células de Schwann/fisiología , Proteínas de Pez Cebra/deficiencia , Pez Cebra/embriología , Animales , Animales Modificados Genéticamente , Artrogriposis , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Ojo/embriología , Ojo/patología , Inmunohistoquímica , Hibridación in Situ , Etiquetado Corte-Fin in Situ , Microscopía Electrónica de Transmisión , Neuronas Motoras/patología , Neuronas Motoras/fisiología , Proteína Básica de Mielina/metabolismo , Células-Madre Neurales/patología , Células-Madre Neurales/fisiología , Proteínas de Unión al ARN/genética , Rombencéfalo/embriología , Rombencéfalo/patología , Células de Schwann/patología , Análisis de Supervivencia , Proteínas de Pez Cebra/genéticaRESUMEN
Excitatory transmission in the brain is commonly mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In amyotrophic lateral sclerosis (ALS), AMPA receptors allow cytotoxic levels of calcium into neurons, contributing to motor neuron injury. We have previously shown that oculomotor neurons resistant to the disease process in ALS show reduced AMPA-mediated inward calcium currents compared with vulnerable spinal motor neurons. We have also shown that PTEN (phosphatase and tensin homolog deleted on chromosome 10) knockdown via siRNA promotes motor neuron survival in models of spinal muscular atrophy (SMA) and ALS. It has been reported that inhibition of PTEN attenuates the death of hippocampal neurons post injury by decreasing the effective translocation of the GluR2 subunit into the membrane. In addition, leptin can regulate AMPA receptor trafficking via PTEN inhibition. Thus, we speculate that manipulation of AMPA receptors by PTEN may represent a potential therapeutic strategy for neuroprotective intervention in ALS and other neurodegenerative disorders. To this end, the first step is to establish a fibroblast-iPS-motor neuron in vitro cell model to study AMPA receptor manipulation. Here we report that iPS-derived motor neurons from human fibroblasts express AMPA receptors. PTEN depletion decreases AMPA receptor expression and AMPA-mediated whole-cell currents, resulting in inhibition of AMPA-induced neuronal death in primary cultured and iPS-derived motor neurons. Taken together, our results imply that PTEN depletion may protect motor neurons by inhibition of excitatory transmission that represents a therapeutic strategy of potential benefit for the amelioration of excitotoxicity in ALS and other neurodegenerative disorders.
Asunto(s)
Fibroblastos/enzimología , Células Madre Pluripotentes Inducidas/enzimología , Neuronas Motoras/enzimología , Células-Madre Neurales/enzimología , Fosfohidrolasa PTEN/metabolismo , Receptores AMPA/metabolismo , Adulto , Animales , Supervivencia Celular , Células Cultivadas , Agonistas de Aminoácidos Excitadores/toxicidad , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibroblastos/trasplante , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/patología , Células Madre Pluripotentes Inducidas/trasplante , Potenciales de la Membrana , Ratones , Ratones Endogámicos NOD , Ratones SCID , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/patología , Neuronas Motoras/trasplante , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/patología , Células-Madre Neurales/trasplante , Fosfohidrolasa PTEN/genética , Cultivo Primario de Células , Interferencia de ARN , Transducción de Señal , Transmisión Sináptica , Teratoma/enzimología , Teratoma/genética , Teratoma/patología , Factores de Tiempo , Transfección , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/toxicidadRESUMEN
Astrocytes emerge as key players in motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). Whether astrocytes cause direct damage by releasing toxic factors or contribute indirectly through the loss of physiological functions is unclear. Here we identify in the hSOD1(G93A) transgenic mouse model of ALS a degenerative process of the astrocytes, restricted to those directly surrounding spinal motor neurons. This phenomenon manifests with an early onset and becomes significant concomitant with the loss of motor cells and the appearance of clinical symptoms. Contrary to wild-type astrocytes, mutant hSOD1-expressing astrocytes are highly vulnerable to glutamate and undergo cell death mediated by the metabotropic type-5 receptor (mGluR5). Blocking mGluR5 in vivo slows down astrocytic degeneration, delays the onset of the disease and slightly extends survival in hSOD1(G93A) transgenic mice. We propose that excitotoxicity in ALS affects both motor neurons and astrocytes, favouring their local interactive degeneration. This new mechanistic hypothesis has implications for therapeutic interventions.
Asunto(s)
Esclerosis Amiotrófica Lateral/patología , Astrocitos/patología , Animales , Astrocitos/efectos de los fármacos , Astrocitos/enzimología , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Activación Enzimática/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamatos/farmacología , Humanos , Vértebras Lumbares/enzimología , Ratones , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/enzimología , Neuronas Motoras/patología , Proteínas Mutantes/metabolismo , Piridinas/administración & dosificación , Piridinas/farmacología , Receptor del Glutamato Metabotropico 5 , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/enzimología , Esferoides Celulares/patología , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1RESUMEN
The effects of a long-term therapy with quinapril on plasma renin activity, plasma aldosterone, atrial natriuretic peptide and left ventricular mass were analysed in patients with mild to moderate systemic hypertension. Fifteen patients (4 women) were treated for one year with quinapril 10 or 20 mg once daily, reducing hereby the systolic and diastolic blood pressure from 167.5 +/- 11.3 to 141 +/- 6.7 mmHg p < 0.001 and from 105.3 +/- 5 to 90 +/- 7 mmHg respectively, within the first two weeks. Blood pressure remained stable during the following 52 weeks. After 6 and 52 weeks of therapy, as expected, we observed an increase of plasma renin activity, plasma aldosterone decrease from 262.6 +/- 88.1 to 178.8 +/- 79.9 p = 0.01 and to 170.3 +/- 64.3 ng/ml p = 0.006 respectively. Atrial natriuretic peptide levels were not significantly altered. After 52 weeks of treatment left ventricular mass index decreased from 107.9 +/- 16.2 to 90.1 +/- 13.4 g/m2 p = 0.0001. It is concluded that treatment with quinapril for 1 year in addition to controlling blood pressure also reduced left ventricular mass probably by a favourable effect on renin-angiotensin-aldosterone system.
Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Isoquinolinas/uso terapéutico , Tetrahidroisoquinolinas , Factor Natriurético Atrial/sangre , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Humanos , Hipertensión/sangre , Masculino , Quinapril , Sistema Renina-Angiotensina/efectos de los fármacos , Método Simple CiegoRESUMEN
OBJECTIVE: To test the hypothesis that heavy smoking may interfere with the variation in ambulatory blood pressure (ABP) and sympathetic nervous system in essential hypertension. METHODS: We compared the office and 24-hour ABP of 48 untreated hypertensive smokers (> 20 cigarettes daily) with 90 non-smoking hypertensives matched for age, sex and body mass index. ABP was recorded using fully automatic SpaceLabs 90,207 units set to take a measurement every 15 minutes during the day (7.00 a.m.-10.00 p.m.) and every 20 minutes during the night (10.00 p.m.-7.00 a.m.). Urine collection for urinary sodium, potassium, epinephrine and norepinephrine excretion was performed during the 24-hour period of ABP monitoring. Catecholamines were measured by high pressure liquid chromatography. RESULTS: The office blood pressure readings of the smoking and non-smoking groups were 156.7/103.4 and 156.5/103.9 mmHg respectively. During the day-time period, ambulatory systolic and diastolic blood pressure was significantly higher in the smokers (146 +/- 12 vs 140.4 +/- 13 mmHg, p < 0.02; 96.4 +/- 8.15 vs 93.1 +/- 10 mmHg, p < 0.05 respectively). This difference was greater among patients under the age of 50 (145.9 +/- 13 vs 136.6 +/- 11 mmHg, p < 0.001 and 97.1 +/- 8.7 vs 92.3 +/- 9.9 mmHg, p < 0.02). Blood pressure during the night-time period did not differ between the two groups (130.5/81.3 vs 126.3/79.5). No differences were detected among the groups as far as urinary catecholamine excretion is concerned. CONCLUSION: Our data suggest that among hypertensive subjects, smokers maintain a higher day-time ambulatory systolic and diastolic blood pressure than non-smokers, particularly in the younger patients, even though casual blood pressure is similar.
Asunto(s)
Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Fumar/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Biomarcadores/orina , Monitoreo Ambulatorio de la Presión Arterial , Epinefrina/orina , Femenino , Humanos , Hipertensión/orina , Masculino , Persona de Mediana Edad , Norepinefrina/orina , Fumar/orinaRESUMEN
We have determined, in a group of patients suffering from massive pulmonary embolism, the ANF basic levels and the changes noticeable in anticoagulant treatment. The heparin therapy, in six patients studied, has produced a considerable clinic and functional better conditions as testified by the gradual improving from hypoxemia. The PaO2, in fact, increases from a basic value of 68.7 +/- 17.65 mmHg to 74.68 +/- 7.16 mmHg on the 7th day (p: n.s.) and to 83.66 +/- 12.46 mmHg on the 14th day (p < 0.05 on the basic value) of treatment. At the same time it has been possible to note a decreasing of plasmatic ANF mean concentrations with decrease from a basic value of 250 pg/ml to 190 pg/ml (p: n.s.) after 7 days to 185 pg/ml (p: n.s.) after 14 days of therapy. However the presents of the high values after 14 days, could be considered as evidence of a persisting change of pulmonary arterious circulation. On the basis of such notes we have tied to compare the amount of ANF, in basic conditions, with the degree of scintigraphic alterations. Of the three patients whose PRA had been previously valued (n. 4, 5, 6), n. 4 and n. 5 showed, in basic condition, a suppression of PRA and only n. 5, at the end of treatment, reached a normal range of PRA. In those three patients there hasn't been relevant changes of plasmatic aldosterone concentration during the study.
Asunto(s)
Anticoagulantes/uso terapéutico , Factor Natriurético Atrial/sangre , Heparina/uso terapéutico , Embolia Pulmonar/sangre , Embolia Pulmonar/tratamiento farmacológico , Enfermedad Aguda , Anciano , Factor Natriurético Atrial/efectos de los fármacos , Femenino , Humanos , Masculino , Factores de TiempoRESUMEN
We have considered the behaviour of the atrial natriuretic factor (ANF) in eight patients suffering from chronic obstructive pulmonary disease (COPD), who have been treated with aminophylline for 24 hours. The mean of ANF concentration decreased from a basic value of 171.31 pg/ml to a value of 128.83 pg/ml (p: n.s.) after treatment. With the exception of patient n. 5 and 7, in the remaining group a significant inverse correlation between ANF and aldosterone was found in accordance with the powerful inhibitory action exerted by the ANF on the secretion of the mineralocorticoid hormone. The changes of the ANF, after a treatment with aminophylline, are characterized by considerable differences among the several patients. In all patients who had a very high basic value, we generally assist to a plasmatic concentration reduction of the hormone after methylxantine. It can be assumed that the reduction of the pulmonary arterial pressure owing to the direct vessel-dilating action of the methylxantine as well as to the effect of vein-dilating and diuretic action reduce the stimulus to the secretion of ANF.
Asunto(s)
Factor Natriurético Atrial/sangre , Broncodilatadores/uso terapéutico , Bronconeumonía/sangre , Bronconeumonía/tratamiento farmacológico , Teofilina/uso terapéutico , Adulto , Anciano , Factor Natriurético Atrial/efectos de los fármacos , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de RemisiónRESUMEN
A case of 17-alpha-hydroxylase deficiency in a genotypic male is described. The patient, who had grown up as a female, at the age of 18 years by chance was seen for enteritis. She presented primary amenorrhea and lack of secondary sexual characteristics combined with hypertension and mild hypokalemia due to excess of mineralcorticoids. The hormonal profile observed under basal conditions was evocative of a deficiency in 17-alpha-hydroxylase. High plasma aldosterone concentrations, in the face of suppressed PRA, were related to interference in RIA method: low plasma aldosterone values were observed when HPLC separation was applied. Eunucoid appearance and gigantism (195 cm) has rarely been observed as a fenotypic expression of this enzymatic deficit, but are justified by deficiency of both androgens and estrogens.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Trastornos del Desarrollo Sexual/diagnóstico , Trastornos del Desarrollo Sexual/enzimología , Adolescente , Aldosterona/sangre , Diagnóstico Diferencial , Trastornos del Desarrollo Sexual/sangre , Trastornos del Desarrollo Sexual/complicaciones , Femenino , Genotipo , Gigantismo/etiología , Humanos , MasculinoRESUMEN
In normal subjects increasing atmospheres of absolute pressure (ATA) on the cardiopulmonary system, in a hyperbaric chamber, results in a marked diuresis and an increase of circulating concentration of atrial natriuretic peptide (ANP). The present investigation was designed to determine the effect of ATA in a group of 5 sodium-retaining cirrhotic patients on hydro-saline balance, renin-angiotensin-aldosterone system and ANP. After seven days on a 10 mEq sodium intake, each patient was studied on both a control and experimental (4-hour stay at 2-ATA in hyperbaric chamber) day. On each day, measurement of the following were obtained: plasma ANP, plasma renin activity (PRA) and aldosterone, electrolytes, creatinine clearance, volume and sodium and potassium urinary excretion. The increasing ATA lacked to induce both diuresis, natriuresis and increase in ANP plasma concentration. In these patients baseline, pre-hyperbaric, mean levels of PRA, aldosterone and ANP were 15.5 +/- 11.5 ng/ml/h, 808.4 +/- 360 pg/ml, 86 +/- 10.1 pg/ml, respectively, and were significantly elevated compared with normal range for control subjects without sodium restriction. In conclusion, increasing pressure at 2-ATA, in a hyperbaric chamber is unable to elicit both diuresis and natriuresis as well as modification on ANP and renin-angiotensin-aldo-sterone system in sodium-retaining cirrhotic patients.
Asunto(s)
Ascitis/sangre , Ascitis/fisiopatología , Presión Atmosférica , Factor Natriurético Atrial/sangre , Oxigenoterapia Hiperbárica , Cirrosis Hepática/sangre , Cirrosis Hepática/fisiopatología , Natriuresis/fisiología , Anciano , Cámaras de Exposición Atmosférica , Femenino , Humanos , Persona de Mediana Edad , Renina/sangre , Factores de TiempoRESUMEN
A patient with hypertension (female: aged 48 years) associated with primary hyperparathyroidism and left renal artery thrombosis is described. Taking into account that the patient was treated on the left side by lithotripsy about two years before the development of hypertension while assuming an oral dose of an estro-progestinic compound, a possible role of these two conditions is discussed in the genesis of renal artery thrombosis and development of renal hypertension.
Asunto(s)
Hiperparatiroidismo/etiología , Hipertensión Renovascular/etiología , Litotricia/efectos adversos , Obstrucción de la Arteria Renal/etiología , Trombosis/etiología , Estrógenos/efectos adversos , Estrógenos/uso terapéutico , Femenino , Humanos , Hiperparatiroidismo/complicaciones , Hipertensión Renovascular/complicaciones , Hipertensión Renovascular/diagnóstico por imagen , Cálculos Renales/terapia , Persona de Mediana Edad , Progesterona/efectos adversos , Progesterona/uso terapéutico , Radiografía , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/diagnóstico por imagen , Trombosis/diagnóstico por imagenRESUMEN
A case of primary hyperparathyroidism with prevalent neuromuscular symptoms is described. Clinical, diagnostic and therapeutic implications are emphasized. Particular attention must involve a full clinical examination, electromyographic data and neuromuscular biopsy to make differentiation from primary myopathy or denervation pathology. Some similarity of electromyographic data with those observed in botulism and myastenia gravis should also be taken in mind. Hypercalcemia could play a pathological role in conditioning abnormalities of nervous impulse conduction at the level of neuromuscular junction. Another possible interference might be related to a direct effect of parathormone and hypophosphataemia on nervous impulse conduction. "Glandular hyperplasia", as observed in this case at istologic examination, rises some problems as far as the prognosis is concerned.
Asunto(s)
Hiperparatiroidismo/complicaciones , Enfermedades Neuromusculares/etiología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: The relationship between plasma atrial natriuretic peptide (ANP), renin-angiotensin-aldosterone system and left ventricular mass in essential hypertension was assessed. PATIENTS AND METHODS: Immunoreactive ANP in 10 normal subjects and 20 untreated patients with mild to moderate essential hypertension was compared with echocardiographic measurement of cardiac size, function and blood pressure. Venous plasma concentrations of ANP were also studied in relation to urinary sodium and potassium excretion, as well as the renin-angiotensin-aldosterone system. RESULTS: Plasma ANP was higher in hypertensive patients (25.3 +/- 13.3 pg/ml; p = 0.003) than normotensive subjects (11.1 +/- 2.7 pg/ml). In hypertensive patients, plasma ANP was inversely related to plasma renin activity (PRA) (r = -0.6; p = 0.009). No relationship was found between ANP and blood pressure, nor between the indices of left ventricular mass and function or urinary electrolytes. CONCLUSIONS: This study showed that circulating ANP is, in average, significantly increased in hypertensive patients, consistent with previous reports. Our data do not support a direct link between left ventricular mass and increased plasma ANP levels in hypertensive patients. Whether the inverse relationship between ANP and PRA in this pathologic state is a direct one or merely a secondary association has not been clearly established.
Asunto(s)
Factor Natriurético Atrial/sangre , Hipertensión/sangre , Hipertrofia Ventricular Izquierda/sangre , Renina/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The subjects were 30 patients with mild-to-moderate hypertension randomly assigned to receive 10 mg of nitrendipine twice daily or 60 mg of diltiazem thrice daily for 14 days. On days 1 and 14 the patients performed an effort test (to a maximum of 100 W) before and after drug administration. Both nitrendipine and diltiazem reduced systolic and diastolic blood pressure; after 14 days of treatment, the reductions in blood pressure were significantly greater in the nitrendipine-treated patients than in the diltiazem-treated patients. Blood pressures were reduced at maximum effort in both treatment groups before drug administration on day 14 compared with day 1. Two hours after drug administration on days 1 and 14, the reductions in effort blood pressures were significantly greater after nitrendipine than after diltiazem. No side effects were noted in either group. It is concluded that nitrendipine is safe and effective in patients with mild-to-moderate hypertension at rest and during exercise.
Asunto(s)
Diltiazem/uso terapéutico , Hipertensión/tratamiento farmacológico , Nitrendipino/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Descanso , Factores de TiempoRESUMEN
The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane.
Asunto(s)
Epoprostenol/biosíntesis , Hipertensión/tratamiento farmacológico , Ketanserina/farmacología , Riñón/efectos de los fármacos , Tromboxano A2/biosíntesis , 6-Cetoprostaglandina F1 alfa/orina , Adulto , Anciano , Femenino , Humanos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Sistema Renina-Angiotensina/efectos de los fármacos , Tromboxano B2/orinaRESUMEN
The authors, following recent observation of two cases of renovascular hypertension, one related to single right renal artery stenosis and the other to fibromuscular dysplasia of the left renal artery, examine the value of the Captopril-Test and treatment with Percutaneous Transluminal Angioplasty (PTA), in the diagnosis and therapy of this form of hypertension. According to the latest experience, reported in the literature, the Captopril-Test yields valid information as regards the dependence of hypertension on the renin-angiotensin system, while PTA represents the primary procedure in the treatment of renovascular hypertension when some conditions are satisfied as in our cases.
Asunto(s)
Angioplastia de Balón , Arteriopatías Oclusivas/complicaciones , Displasia Fibromuscular/complicaciones , Hipertensión Renovascular/terapia , Adulto , Femenino , Displasia Fibromuscular/patología , Humanos , Hipertensión Renovascular/etiologíaRESUMEN
The study was designed to compare the efficacy of captopril and enalapril, both orally active inhibitors of angiotensin converting enzyme, in the treatment of primary hypertension when administered in a single daily dose. After placebo washout for two weeks, 20 hypertensive patients (I-II class, according to WHO), were admitted to active treatment, in a randomized sequence, with captopril (50 mg) and enalapril (20 mg) once a day in the morning (8 a.m.). Supine and erect blood pressure and heart rate were measured weekly, 24 hours after drug administration by using a mercury standard sphygmomanometer. In all patients ambulatory noninvasive blood pressure monitoring was performed after 4 weeks of treatment. The data confirmed the efficacy of both drugs in lowering blood pressure. However, while the antihypertensive effect of enalapril was prolonged throughout 24 hours, captopril was effective only for about 22 hours, a period longer than previously suggested on the basis of serum ACE inhibition, but not sufficient to cover the whole day. Therefore, if captopril therapy has to be used in a single daily dose an attempt should be made using an increased dosage or by employing the drug in some retarded pharmaceutical form. The need to prolong the antihypertensive effect of captopril to 24 hours is based on the clinical experience according to which the smaller the number of tablets to be taken the better the compliance. This is particularly true for cases of asymptomatic hypertension which nevertheless require lifelong therapy.
Asunto(s)
Captopril/uso terapéutico , Enalapril/uso terapéutico , Hipertensión/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Captopril/administración & dosificación , Evaluación de Medicamentos , Enalapril/administración & dosificación , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Distribución AleatoriaRESUMEN
The antihypertensive effect of ketanserin, a recent 5-hydroxytryptamine (5-HT) antagonist, which acts on the 5-HT2-subtype receptor, was evaluated in 10 patients of both sexes (age range 35-69 years) with mild to moderate essential hypertension. Blood pressure and heart rate were measured at rest, in supine and standing position at the end of two weeks of placebo washout and after 2, 4 and 8 weeks of treatment with ketanserin 20 mg twice daily as monotherapy, while the changes of blood pressure and heart rate during static (hand-grip) and dynamic (bicycle ergometer) exercise were evaluated at the end of placebo and of the fourth week of therapy. The treatment induced a highly significant reduction of supine and standing systolic and diastolic blood pressure during rest, without any significant change in heart rate. During dynamic exercise, the increase in systolic and diastolic blood pressure and heart rate was not blunted by ketanserin, while the drug reduced systolic blood pressure and heart rate increase, during static exercise, with no change of diastolic blood pressure. From these data it may be concluded that ketanserin lowers blood pressure in essential hypertension without any interference with cardiovascular reflexes related to standing or dynamic exercise, and reduces the increase of systolic blood pressure and heart rate during static exercise with favourable interference on myocardial oxygen consumption. This sparing effect on myocardial oxygen demand is particularly relevant in hypertensive patients with asymptomatic coronary disease engaged in normal daily physical activity which includes many forms of static exercise.