Modelos de hipertensäo arterial / Experimental models of arterial hypertension

Existe uma busca extenuante, por parte dos pesquisadores, de um modelo experimental que possa melhor caracterizar uma patologia täo importante para o ser humano como a hipertensäo essencial. Dentre os modelos genéticos de hipertensäo säo analisados os ratos com hipertensäo espontânea (SHR) e a cepa de ratos sensíveis à ingestäo de sódio (Dahl). Entre os modelos de hipertensäo neurogênica säo discutidos aqueles que envolvem a lesäo do núcleo do trato solitário (NTS), e o da deaferentaçäo sino-aórtica, associada, ou näo, à desnervaçäo das aferências cardiopulmonares. Entre as hipertensöes renais foram destacadas: a renovascular que decorre da oclusäo parcial da artéria renal; a renopriva, como o próprio nome indica; a perinefrítica que decorre da induçäo de fibrose renal pelo envolvimento do rim com um abrasivo contido por um tecido; e liberaçäo do pedículo renal após algumas horas de oclusäo total. O modelo de constriçäo (parcial ou total) da aorta abdominal examina os fatores mecânico e heurohumorais na elevaçäo da pressäo arterial. Um modelo descrito mais recentemente, que é examinado, é o do bloqueio da formaçäo de óxido nítrico (NO) com o L-NAME. E, finalmente, é apresentado o modelo de hipertensäo induzida pelo tratamento com deoxicorticosterona associado à ingestäo alta de sódio.

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factores and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1 percent NaCl and 0.03 percent KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 + 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 + 0.01 mg/g) compared to control (1.92 + 0.04 and 0.48 + 0.01 mg/g, respectively) rats. MAP was significantly higher (39 percent) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 + 0.03 mg/g) and RVW/BW (0.52 + 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity.

Effects of intracerebroventricular infusion of angiotensin II and related peptides on water and sodium ingestion and excretion

The objetive of the present study was to investigate the effects of an angiotensin II (AII) analogue, Des-Asp1-AII and of two competitive blockers, [Leu8]-AII and [octanoyl-Leu8]-AII, infused intracerebroventriculary on the ingestion of water and of a 3% NaCl solution, as well as on diuresis and natriuresis in normal rats and in adrenalectomized and deoxycorticosterone (DOCA)-treated rats. Both AII and Des-Asp1-AII increased water and 3% NaCl intake and increased urine and Na+ excretion, the effect of AII being more intense. Except for 3% NaCl, the responses of all other parameters were totally or partially reduced by previous treatment with [Leu8]-AII or [octanoyl-Leu8]-AII. Subcytaneous DOCA injection caused water ingestion. Previous treatment with DOCA increased the response to AII for the ingestion of 3% NaCl and inhibited sodium excretion. The results obtained for adrenalectomized rats treated with DOCA, AII and analogous agonists did not differ from those observed in normal rats. These data suggest a possible synergism between the cerebral and renal renin-angiotensin systems in the regulation of the physiological parameters studied

Effects of intracerebroventricular infusion of angiotensin II and related peptides on water and sodium ingestion and excretion.

The objective of the present study was to investigate the effects of an angiotensin II (AII) analogue, Des-Asp1-AII and of two competitive blockers, [Leu8]-AII and [octanoyl-Leu8]-AII, infused intracerebroventricularly on the ingestion of water and of a 3% NaCl solution, as well as on diuresis and natriuresis in normal rats and in adrenalectomized and deoxycorticosterone (DOCA)-treated rats. Both AII and Des-Asp1-AII increased water and 3% NaCl intake and increased urine and Na+ excretion, the effect of AII being more intense. Except for 3% NaCl, the responses of all other parameters were totally or partially reduced by previous treatment with [Leu8]-AII or [octanoyl-Leu8]-AII. Subcutaneous DOCA injection caused water ingestion. Previous treatment with DOCA increased the response to AII for the ingestion of 3% NaCl and inhibited sodium excretion. The results obtained for adrenalectomized rats treated with DOCA, AII and analogous agonists did not differ from those observed in normal rats. These data suggest a possible synergism between the cerebral and renal renin-angiotensin systems in the regulation of the physiological parameters studied.

Hiperplasia suprarrenal virilizante: revisión de 23 años 1963-1986 / Virilizing adrenal hyperplasia: revision of 23 years (1963-1986)

Se analiza una casuística de 27 casos de hiperplasia suprarrenal virilizante reunidos entre 1963 y 1986, de los cuales 23 son de sexo femenino y 4 masculinos. El 63% fueron diagnosticados dentro del primer mes de vida y el 22% después del primer año. La principal causa de consulta fue la de sexo ambiguo siendo también frecuente la hipertrofia del clítoris. Los principales exámenes de laboratorio fueron, 17 cetoesteroides y pregnantriol urinarios; 17 hidroxiprogesterona y electrólitos plasmáticos. El tratamiento actual consiste en cortisol 20 a 30 mg por metro cuadrado y por día en 3 dosis más 9 alfa-fluor-hidrocortisona 0,05 a 0,15 mg diario. En casos de descompensación con desequilibrio electrolítico hay que reponer sodio y administrar Doca (1 a 2 mg intramuscular cada 12 horas) e hidrocortisona (50 a 100 mg endovenoso). La letalidad del grupo estudiado fue de 33% destacando las infecciones entre las causas de muerte más frecuentes

Evoluçäo clínica de 14 casos de hiperplasia congênita de supra-renal por deficiência da 21-hidroxilase / Clinical course of 14 cases of congenital adrenal hyperplasia due to 21-hydroxylase dificiency

Os autores apresentam os resultados do seguimento clínico (1966 a 1982) de 14 pacientes portadores de hiperplasia congênita da supra-renal por deficiência de 21-hidroxilase, sendo sete casos portadores da forma perdedora de sal e sete da forma näo perdedora. Doze pacientes eram do sexo feminino e dois do sexo masculino. As idades variaram de um mês a 12 anos e 11 meses. Os parâmetros estudados foram: estatura, peso, idade óssea, 17 alfa-hidroxiprogesterona e 17 ceto-esteróides plasmáticos. Os resultados demonstraram, que os casos mais antigos, devido à impossibilidade de seguimento laboratorial adequado, apresentaram má evoluçäo quanto ao crescimento, tendo em vista a aceleraçäo da idade óssea

Glucocorticoid treatment of girls with congenital adrenal hyperplasia: effects on height, sexual maturation, and fertility.

Ninety-eight females with congenital adrenal hyperplasia due to a defect in either the 21-hydroxylase or the 11 beta-hydroxylase enzyme were evaluated to determine the effects of glucocorticoid treatment on growth, pubertal development, and fertility. When treatment was begun prior to one year of age, mean final height was 157.4 +/- 7.3 com, well within the normal adult female range, and significantly (p less than 0.001) greater than the mean final height of 150.9 +/- 4.3 cm found in untreated patients. The mean age of menarche in patients treated prior to the age of six years was 13.8 +/- 3.7 years which is significantly (p less than 0.01) delayed compared to that in the normal population of the United States. However, 92% of patients with menstrual delay had inadequate suppression of adrenal androgens and urinary excretion of 17 ketosteroids larger than 7.0 mg/24hours. The increased production of adrenal androgens was the result of poor compliance or an insufficient prescribed dose of glucocorticoids. The fertility rate in patients first treated between six and 20 years of age was 64%. The excretion of urinary 17 KS at the time of pregnancy was 2.5 to 5.3 mg/24 hours. All of the patients who delivered term infants required delivery by cesarean section because of cephalopelvic disproportion. The major problems encountered in the management of adolescent patients were patient noncompliance and physician failure to increase the glucocorticoid dose as the patient's body size increased.

Electrolyte metabolism of muscle in the salt-losing form of congenital adrenal hyperplasia.

The study of metabolism of muscle electrolyte in children with the salt-losing form of congenital adrenal hyperplasia reveals two types of alterations. After admission and during initial therapy with salt and desoxycorticosterone, the changes are typical of those seen in experimental animals with adrenalectomy and excessive replacement therapy. Discontinuation of the sodium supplement after three months of therapy resulted in a return of muscle electrolyte values to normal. During the period of poor growth common to these patients a different pattern was observed. Sodium and water accumulated without alteration in tissue potassium. The mechanism of this alteration is not clear; however, it is consistent with the known effects of excess cortisone on muscle composition. These observations permit the conclusion that at least two fractions of sodium are present in muscle fibers, that which exchanges potassium and that which is independent of potassium metabolism.

Familial congenital absence of adrenal glands; evaluation of glucocorticoid, mineralocorticoid, and estrogen metabolism in the perinatal period.

The patient was the fourth of affected male siblings. Cortisol (1.3 micrograms per cent), cortisone (9.6), and corticosterone sulfate (0.1) concentrations were low in cord blood. The larger amount of cortisone may have originated from maternal cortisol. Aldosterone was undetectable in cord blood, indicating lack of fetal secretion or maternofetal transfer. Unexpectedly normal concentrations of 11-deoxycorticosterone (DOC) sulfate in cord serum could represent maternal transfer of DOC, with subsequent fetal sulfurylation. Low estrone and estradiol concentrations in maternal and cord serum were consistent with absence of the fetal adrenals. Despite the low levels of the steroids, the propositus had a normal lecithin-sphingomyelin ratio at 38 weeks' gestation. Circulatory insufficiency developed within half an hour after birth and responded to gluco- and mineralocorticoid therapy. The three untreated siblings died between 14 and 67 hours of age. It is evident that early recognition of this condition may be lifesaving.