RESUMEN
Angiotensin II was infused into conscious rabbits at various doses from 0.001 to 0.5 microgram . kg-1 . min-1 for 24 h, and caused multifocal myocardial necrosis, renal tubular necrosis and acute renal failure. The myocardial necroses were found principally in the left ventricle; only at the highest doses of angiotensin II were right ventricular lesions present. The endocardium was not involved and no arterial or arteriolar lesions were seen. Mean arterial plasma angiotensin II concentration during angiotensin infusion was closely correlated with the increase in arterial pressure, the height of the plasma urea at the end of the infusion and the severity of the induced myocardial lesions. The myocardial necroses could be a consequence of the induced hypertension, or a direct effect of angiotensin II, or a combination of effects, although their predominance in the left ventricle suggests high systemic arterial pressure is an important factor. Cardiac lesions were observed with plasma angiotensin II concentrations only some 2 to 3 fold normal values; it is therefore possible that similar myocardial abnormalities might occur as a result of rises in endogenous renin, for example, in experimental or clinical renovascular hypertension.
Asunto(s)
Lesión Renal Aguda/patología , Angiotensina II/sangre , Cardiomiopatías/patología , Lesión Renal Aguda/sangre , Animales , Presión Sanguínea , Cardiomiopatías/sangre , Ventrículos Cardíacos/patología , Necrosis Tubular Aguda/sangre , Necrosis Tubular Aguda/patología , Necrosis , ConejosRESUMEN
The possibility that the responsiveness of plasma aldosterone concentration to angiotensin II alters with changes in sodium balance was investigated in male beagle dogs under conditions of controlled sodium and potassium intake. Angiotensin II was infused at four different rates (usually 3, 6, 12, and 24 ng/kg/min), each for 1 h, 1) after periods of normal sodium diet (32 mEq/day), 2) after moderate sodium depletion (negative cumulative sodium balance 25-58 mEq), 3) after severe sodium depletion (65-116 mEq negative cumulative sodium balance), and 4) after sodium loading (150-212 mEq positive sodium balance), daily potassium intake remaining constant (26 mEq/day) throughout. Angiotensin II/aldosterone dose-response curves after moderate sodium depletion were both elevated and steepened in comparison with those found during normal sodium intake. Severe sodium depletion was associated with even greater elevation of dose-response curves, but individual aldosterone responses to angiotensin II were irregular and unpredictable. Sodium loading significantly diminished aldosterone responsiveness to angiotensin II. Blood pressure increments during angiotensin II infusion were attenuated by sodium depletion.
Asunto(s)
Aldosterona/farmacología , Angiotensina II/farmacología , Sodio/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Glucosa/farmacología , Masculino , Sodio/farmacologíaRESUMEN
There is clinical, biochemical, and pathological evidence that idiopathic aldosteronism is part of a continuum which includes low-renin and normal-renin essential hypertension. In a retrospective statistical study, 89 patients with essential hypertension have been compared with 22 cases of idiopathic aldosteronism and 34 cases of aldosterone-secreting adrenal adenomas. Measurements of serum sodium, potassium, bicarbonate, and plasma angiotensin II concentrations and estimates of exchangeable sodium and potassium were obtained for individual patients. By using various combinations of these biochemical variables, a statistic, the Mahalanobis distance, was described for each of the three populations, essential hypertension, idiopathic aldosteronism, and adrenal adenomas. For each combination of variables, the distribution of the idiopathic aldosteronism group resembled that of the essential hypertension group more closely than that of the aldosterone-secreting adrenal adenoma group. Thus, the use of this statistical technique provides further evidence of the similarity of essential hypertension and idiopathic aldosteronism.
Asunto(s)
Hiperaldosteronismo/metabolismo , Hipertensión/metabolismo , Adenoma/metabolismo , Neoplasias de las Glándulas Suprarrenales/metabolismo , Adulto , Aldosterona/sangre , Angiotensina II/sangre , Bicarbonatos/sangre , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Potasio/sangre , Renina/sangre , Sodio/sangre , Estadística como Asunto , Ácido Vanilmandélico/orinaRESUMEN
A small double-blind pilot study was carried out to assess whether captopril treatment in hypertension has a euphoriant effect. Eight patients were maintained on constant therapy of atenolol and bendrofluazide for at least 4 weeks before and throughout the study. Captopril 25 mg three times daily or matching placebo was administered double-blind for 6 weeks, with crossover to placebo or captopril from Weeks 7 to 12. Psychiatric assessment was made at Weeks 3, 6, 9, and 12. During the captopril phase, blood pressure was reduced, plasma angiotensin II lowered, and plasma renin raised. Mood was slightly, but significantly, lower during captopril administration; thus, there was no evidence of an euphoriant effect of captopril. This pilot trial also indicates the feasibility of the approach, and such studies of hypertensives under therapy should be usefully extended and refined.
Asunto(s)
Captopril/uso terapéutico , Hipertensión/tratamiento farmacológico , Prolina/análogos & derivados , Método Doble Ciego , Evaluación de Medicamentos , Euforia , Femenino , Humanos , Hipertensión/psicología , Masculino , Persona de Mediana Edad , Placebos , Encuestas y CuestionariosRESUMEN
An ampouled preparation of human atrial natriuretic factor, ANF-(99-126), was evaluated by 23 laboratories in 10 countries for its suitability to serve as the international standard for ANF. The preparation was calibrated by radioimmunoassay, radioreceptor binding assay, and bioassay and was shown to have satisfactory stability and biological activity. Estimates of the ANF content of a set of specimens of plasma in terms of the standard showed agreement in ranking order when the ANF was extracted prior to assay. However, estimates of the ANF content of the plasmas in terms of either the international standard or the various local standards varied widely among laboratories. On the basis of the results reported here, with the agreement of the participants in the study and with the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 85/669 was established in 1987 as the international standard for ANF, with a defined potency of 2.5 international units per ampoule.
Asunto(s)
Factor Natriurético Atrial/normas , Factor Natriurético Atrial/sangre , Calibración , Estabilidad de Medicamentos , Humanos , Concentración de Iones de HidrógenoRESUMEN
Dose-response curves relating plasma angiotensin II (AII) concentration during AII infusion to blood pressure (BP), to plasma aldosterone, and to plasma 18-hydroxycorticosterone were compared in normal subjects and in patients with essential hypertension, Conn's syndrome, and nontumorous hyperaldosteronism. The BP response was steeper than normal in patients with Conn's syndrome and essential hypertension. Before infusion, mean plasma aldosterone concentration was approximately four-fold higher in Conn's syndrome than in the normal group, while that of 18-hydroxycorticosterone was ninefold higher. Neither increased significantly during AII infusion. In essential hypertension, both corticosteroids were within the normal range, but their responses to AII infusion were greater than normal. In the three subjects with non-tumorous hyperaldosteronism, plasma aldosterone and 18-hydroxycorticosterone concentrations were raised, and their responses to AII infusion resembled those found in essential hypertension and were different from those found in Conn's syndrome. This suggests that nontumorous hyperaldosteronism is not a variant of Conn's syndrome. In the response to AII and in other ways, it is indistinguishable from essential hypertension.
Asunto(s)
18-Hidroxicorticosterona/sangre , Aldosterona/sangre , Angiotensina II/farmacología , Corticosterona/análogos & derivados , Hiperaldosteronismo/fisiopatología , Hipertensión/fisiopatología , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Adulto , Angiotensina II/sangre , Presión Sanguínea , Femenino , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana EdadRESUMEN
The case is reported of a young woman with severe hypertension, unilateral renal artery stenosis, variously normal or marginally high plasma concentrations of active renin, angiotensin II, aldosterone, sodium, and potassium; and normal total exchangeable and total body sodium and potassium. Arteriograms and ureter catheterization showed the stenosis to be severe, but the unstimulated renal vein renin and angiotensin II differential to be modest. Captopril caused an initial fall in angiotensin II and arterial pressure. During prolonged captopril treatment, plasma angiotensin II and aldosterone remained depressed; exchangeable and total body sodium and potassium were unaltered. Blood pressure fell further to normal levels during prolonged captopril treatment, while subsequent surgical correction of the renal artery stenosis was curative; absolute values of blood pressure and plasma angiotensin II were similar in both situations. The findings support, without proving, the concept that chronic modest elevation of angiotensin II may be responsible for sustained hypertension in unilateral renal artery stenosis. Patients of this type contrast sharply with those, also with severe renal artery stenosis or occlusion, who have gross elevation of renin, angiotensin II, and aldosterone, with sodium and potassium deficiency. Captopril or surgery are effective in both syndromes, but the manner of response to treatment differs markedly.
Asunto(s)
Angiotensina II/sangre , Captopril/uso terapéutico , Hipertensión Renal/metabolismo , Hipertensión Renovascular/metabolismo , Prolina/análogos & derivados , Obstrucción de la Arteria Renal/sangre , Adulto , Aldosterona/sangre , Angiotensina II/fisiología , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertensión Renovascular/sangre , Potasio/metabolismo , Obstrucción de la Arteria Renal/tratamiento farmacológico , Obstrucción de la Arteria Renal/cirugía , Renina/sangre , Sodio/metabolismoRESUMEN
A 20-yr-old male was found to have diabetes insipidus is association with panhypopituitarism but without any focal neurological lesion being identified. He was initially treated with steroid supplements, the features of diabetes insipidus being controlled with a thiazide diuretic. Eighteen months later the patient lost thirst sensation and stopped treatment, subsequently being re-admitted with severe dehydration, oliguria and focal neurological signs. Further investigation, including brain biopsy, confirmed the presence of an atypical pinealoma which was considered inoperable. Measurements of plasma antidiuretic hormone (ADH) and angiotensin II (AII) concentrations during the severe dehydration showed very high levels of AII, but inappropriately low plasma ADH levels for the severity of dehydration. We consider that the evidence obtained from this case supports the view that the oliguria with hypertonic urine present during severe dehydration was due to a direct renal action of the very high AII levels, possibly supplemented by the residual ADH secretion.
Asunto(s)
Angiotensina II/uso terapéutico , Diabetes Insípida/tratamiento farmacológico , Hipopituitarismo/tratamiento farmacológico , Orina , Vasopresinas/uso terapéutico , Adulto , Ritmo Circadiano , Deshidratación , Diabetes Insípida/complicaciones , Diabetes Insípida/metabolismo , Hormona del Crecimiento/sangre , Humanos , Hipopituitarismo/complicaciones , Hipopituitarismo/metabolismo , Hipopituitarismo/fisiopatología , Masculino , Concentración Osmolar , Factores de TiempoRESUMEN
A study of plasma arginine vasopressin in 17 patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with bronchogenic carcinoma, revealed that the arginine vasopressin levels were distinctly elevated in most. In 14 patients with bronchogenic carcinoma, but without overt SIADH, plasma levels of arginine vasopressin were significantly higher than in normal subjects (p less than 0.001). This, together with the finding of a lower than normal plasma osmolality in this group, suggests that inappropriate ADH excess might be much more common in patients with bronchogenic carcinoma than previously thought. The normal positive correlation between plasma osmolality and plasma arginine vasopressin was found to be reversed in SIADH. Seven of nine patients with overt SIADH, studied after fluid deprivation, showed an increase in plasma arginine vasopressin coincident with an increase in plasma osmolality (r = +0.8, p less than 0.01); in one patient, plasma arginine vasopressin returned to the original level following rehydration. The possibility that this might imply a degree of physiologic control to what is generally considered an autonomous secretion is discussed. It is, however, considered more likely that other factors, including changes in plasma volume and glomerular filtration, might explain the increase in plasma levels of arginine vasopressin.
Asunto(s)
Arginina Vasopresina/sangre , Carcinoma Broncogénico/sangre , Neoplasias Pulmonares/sangre , Vasopresinas/análogos & derivados , Vasopresinas/sangre , Adulto , Anciano , Carcinoma Broncogénico/complicaciones , Femenino , Humanos , Hiponatremia/complicaciones , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Concentración Osmolar , Síndrome , Privación de AguaRESUMEN
The relationship between endogenous plasma concentrations of atrial natriuretic peptide and renin was examined in resting normal subjects and patients with cardiac impairment. To test the hypothesis that atrial natriuretic peptide inhibits renin secretion, intravenous infusions of atrial natriuretic peptide were administered to normal volunteers, patients with end-stage renal failure, and conscious dogs in both sodium-replete and sodium-depleted states. Plasma atrial natriuretic peptide and renin were inversely related in normal subjects (r = -0.52, n = 140, p less than 0.001), but a weak positive association between these two variables was observed in patients with cardiac impairment (r = 0.32, n = 60, p less than 0.02). Low doses of both 26- and 28-amino-acid human atrial natriuretic peptide (2 pmol/kg/minute for two hours) given to sodium-replete normal subjects halved plasma renin compared with time-matched placebo values (19 +/- 4 and 18 +/- 3 versus 36 +/- 8 microU/ml, p less than 0.001 for both). Incremental doses of synthetic atrial natriuretic peptide suppressed plasma renin below time-matched placebo values in both sodium-replete (maximal suppression 1.2 +/- 0.4 versus 8.6 +/- 1.4 microU/ml, p less than 0.001) and sodium-depleted (maximal suppression 18.9 +/- 4.9 versus 51 +/- 13 microU/ml, p less than 0.05) dogs. This effect was initially apparent at low doses of atrial natriuretic peptide (1 pmol/kg/minute), and renin suppression was maximal, in both states, with lesser doses of atrial natriuretic peptide than those at which maximal natriuresis was observed. Atrial natriuretic peptide administered to patients with end-stage renal failure (10 pmol/kg/minute for one hour) caused no change in plasma renin. These data confirm that atrial natriuretic peptide inhibits renin secretion in a dose-related manner and suggest that this action of the peptide is modified by both the baseline sodium status and renal function of the recipient.
Asunto(s)
Factor Natriurético Atrial/farmacología , Renina/sangre , Adulto , Animales , Factor Natriurético Atrial/sangre , Perros , Cardiopatías/sangre , Humanos , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Sodio en la Dieta/administración & dosificaciónRESUMEN
The converting enzyme inhibitor enalapril, in single daily doses of 10 to 40 mg, was given to 20 hypertensive patients with renal artery stenosis. The decrease in blood pressure six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II, and to the concurrent decrease in angiotensin II. Blood pressure decreased further with continued treatment; the long-term decrease was not significantly related to pretreatment plasma renin or angiotensin II levels. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low, and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, decreased further. The increase in active renin during long-term treatment was proportionately greater than the increase in angiotensin I; this probably reflects the diminution in renin substrate that occurs with converting enzyme inhibition. Long-term enalapril treatment increased renin secretion by more than 10-fold, and renal venous and peripheral plasma renin concentration by more than 20-fold; however, the mean renal venous renin ratio was not changed. Enalapril caused a reduction in effective renal plasma flow via the affected kidney but a marked and consistent increase on the contralateral side, where renal vascular resistance decreased. The overall increase in effective renal plasma flow was significantly related to the decrease in angiotensin II. Overall glomerular filtration rate was lowered, and serum creatinine and urea increased. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight but distinct increases in serum potassium. In five patients with bilateral renal artery lesions, enalapril given alone for three months did not cause renal function to deteriorate. Enalapril was well tolerated and provided effective long-term control of hypertension; only two of the 20 patients studied required concomitant diuretic treatment.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dipéptidos/uso terapéutico , Hipertensión/tratamiento farmacológico , Obstrucción de la Arteria Renal/tratamiento farmacológico , Administración Oral , Adulto , Aldosterona/sangre , Angiotensina I/sangre , Angiotensina II/sangre , Composición Corporal/efectos de los fármacos , Creatinina/sangre , Evaluación de Medicamentos , Enalapril , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Riñón/irrigación sanguínea , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Postura , Potasio/metabolismo , Obstrucción de la Arteria Renal/complicaciones , Renina/sangre , Sodio/metabolismoRESUMEN
Eighteen male Sprague-Dawley rats were fed a sodium-free diet and given NaCl (154 mmol/l) labelled with 22Na (37 Bq/l [1 microCi/l]) to drink. Following equilibration, each had a unilateral nephrectomy; 10 days later the animals started a series of 10 injections of deoxycorticosterone (12.5 mg twice-weekly for 5 weeks). Thereafter the animals were split into two groups, one to continue with DOC injections and diet as previously (DOC-salt), the other to stop DOC injections and continue a sodium-free diet and labelled saline of lower concentration (89 mmol/l) (post-DOC). During the period of DOC injections to both groups, blood pressure and exchangeable sodium rose significantly and were significantly correlated. In the post-DOC group, hypertension persisted and was not significantly different from that in the DOC-salt group. However, in the post-DOC-salt group, exchangeable sodium fell to levels similar to those found in uninephrectomized control animals of similar age which had never been given DOC or a high salt intake and had never been hypertensive. Thus an expanded sodium space does not contribute to maintenance of hypertension in the post-DOC-salt model.
Asunto(s)
Desoxicorticosterona/farmacología , Hipertensión/inducido químicamente , Cloruro de Sodio/farmacología , Sodio/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Dieta Hiposódica , Hipertensión/metabolismo , Masculino , Nefrectomía , Ratas , Ratas Endogámicas , Renina/sangreRESUMEN
Exchangeable and plasma electrolytes, blood pressure and aldosterone were measured in groups of patients with idiopathic hyperaldosteronism, primary hyperaldosteronism and essential hypertension and in normal subjects. In idiopathic hyperaldosteronism exchangeable sodium was higher than in both essential hypertensive and normal groups but lower than in primary hyperaldosteronism. Plasma sodium results were similar except that no difference existed between the two forms of hyperaldosteronism. Plasma potassium concentration was lower in idiopathic hyperaldosteronism than in either essential hypertensive or in normal groups, but higher than in primary hyperaldosteronism. Blood pressure correlated with age in all groups and with exchangeable sodium in hypertensive patients. This was also the case with exchangeable sodium:exchangeable potassium ratio, but blood pressure did not correlate with aldosterone in any group. In idiopathic hyperaldosteronism, as in essential hypertension, sodium and blood pressure correlated strongly in male and weakly in female patients. The analysis reveals important differences between idiopathic and primary hyperaldosteronism and also between idiopathic hyperaldosteronism and essential hypertension.
Asunto(s)
Presión Sanguínea , Hiperaldosteronismo/fisiopatología , Hipertensión/fisiopatología , Potasio/sangre , Sodio/metabolismo , Adulto , Anciano , Femenino , Humanos , Hiperaldosteronismo/sangre , Hiperaldosteronismo/metabolismo , Hipertensión/sangre , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Sodio/sangreRESUMEN
Plasma atrial natriuretic peptide (ANP) concentrations were measured by both direct radio-immunoassay and with pre-extraction of the peptide from plasma using C18 reverse phase columns. Peptide concentrations were measured in normal subjects (including a group of eight volunteers who received an intravenous infusion of 0.9% NaCl solution), patients with renal failure (including a group with end-stage disease undergoing renal dialysis) and patients with a spectrum of cardiac dysfunction. The overall correlation of results from direct and extracted assay methods was good. However, absolute values from extracted assays were significantly lower than from parallel direct assays. This discrepancy was due to interference from platelets and from another, as yet unidentified, plasma component demonstrated by gel filtration experiments. Extraction of the peptide from plasma by C18 columns largely eliminated these sources of interference and was particularly important for accurate measurement of peptide concentrations within the normal range. Plasma peptide concentrations were elevated in cardiac and renal failure, fell with renal dialysis and rose in normal subjects challenged with an intravenous isotonic fluid load. These findings suggest that ANP participates in the regulation of body fluid volumes and arterial pressure.
Asunto(s)
Factor Natriurético Atrial/sangre , Radioinmunoensayo/métodos , Adolescente , Adulto , Tampones (Química) , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Femenino , Cardiopatías/sangre , Humanos , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana EdadRESUMEN
Measurements of exchangeable sodium, arterial pressure and plasma concentrations of active renin, angiotensin II, aldosterone, sodium and potassium were made in 35 hypertensive patients with renal artery stenosis, 30 having unilateral renal arterial lesions. Plasma urea was below 7 mmol/l in 24 of the patients with unilateral lesions. In these and in the whole group of 35 patients there were significant inverse correlations between exchangeable sodium and diastolic blood pressure and between plasma sodium concentration and diastolic pressure. Six patients had hyponatraemia with a plasma sodium concentration less than 135 mmol/l. All were sodium-deplete with secondary hyperaldosteronism, three also having malignant-phase hypertension. Twelve of the patients with unilateral renal artery stenosis underwent bilateral ureteric catheterization. Sodium excretion was greater from the contralateral kidney than from the affected kidney and the rate of sodium excretion from the former, but not from the latter, was significantly related to arterial pressure. The relation of diastolic blood pressure and exchangeable sodium is the opposite of the positive correlation found in essential hypertension and Conn's syndrome. In renal artery stenosis the inverse correlation could result from a natriuretic effect of increased arterial pressure occurring mainly in the contralateral kidney.
Asunto(s)
Hipertensión Renovascular/sangre , Obstrucción de la Arteria Renal/sangre , Sodio/sangre , Adulto , Aldosterona/sangre , Angiotensina II/sangre , Presión Sanguínea , Creatinina/orina , Femenino , Humanos , Hipertensión Renovascular/complicaciones , Hiponatremia/etiología , Masculino , Persona de Mediana Edad , Potasio/sangre , Obstrucción de la Arteria Renal/complicaciones , Renina/sangre , Sodio/orina , Ácido p-Aminohipúrico/orinaRESUMEN
It is reported that dietary deprivation of sodium in young rats produces changes of sodium balance and aldosterone excretion which persist when normal sodium intake is restored. To test this further, sodium intake was reduced 10-fold in rats. In the first experiment sodium intake was reduced for 5 weeks in rats aged 3 weeks. Systolic blood pressure, heart rate and plasma renin concentration increased and growth rate was reduced. Sodium intake was then increased for 10 weeks. Blood pressure, heart rate and plasma renin concentration fell and growth rate increased but body weight did not regain control values. As compared with controls, plasma concentrations of aldosterone and corticosterone did not increase after the 10-week period. Thus, sodium depletion did not produce an irreversible change in aldosterone but it did raise arterial pressure. Further experiments confirmed the pressor effect in young and adult rats. Blood pressure was measured in the tail in these experiments but the increase in pressure was not a technical artifact as measurements made in the tail correlated well with measurements made simultaneously by intra-arterial catheter. Catheters were inserted under general anaesthetic for this comparison of pressure and rats previously deprived of sodium showed a significantly higher mortality rate due to the anaesthesia and surgery involved. Thus, a 10-fold reduction of dietary sodium raises blood pressure in young and adult rats and it may increase mortality from a minor surgical procedure. It does not produce irreversible changes in aldosterone.
Asunto(s)
Presión Sanguínea , Hiperaldosteronismo/sangre , Sodio en la Dieta , Sodio/deficiencia , Aldosterona/sangre , Animales , Peso Corporal , Corticosterona/sangre , Frecuencia Cardíaca , Masculino , Ratas , Ratas Endogámicas , Renina/sangreRESUMEN
Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.
Asunto(s)
Presión Sanguínea , Electrólitos/metabolismo , Hiperaldosteronismo/fisiopatología , Adulto , Aldosterona/sangre , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hiperaldosteronismo/metabolismo , Hipertensión/etiología , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Mineralocorticoides/farmacología , Análisis de Regresión , Sodio/metabolismo , Vasoconstricción , Vasopresinas/fisiologíaRESUMEN
Conscious male beagle dogs were given constant intravenous infusions of noradrenaline for 14 days, four receiving 125 ng/kg/min and four 250 ng/kg/min. Before, during and after these infusions dose-response studies were done in which additional noradrenaline was infused at 500, 1000 and 2000 ng/kg/min, each rate for 1 h. Blood samples were taken before and during infusions for measurement of haematocrit and plasma concentrations of noradrenaline, active renin, angiotensin II, aldosterone, sodium and potassium. Fourteen-day infusion of noradrenaline at 125 ng/kg/min did not raise blood pressure significantly though infusion at 250 ng/kg/min did, but for the first week of infusion only. Heart rate decreased significantly at both rates. Arterial pressure fell markedly and significantly on stopping infusion. Mean plasma concentrations of renin, angiotensin II and aldosterone tended to be lower during prolonged infusion of noradrenaline, but only the fall of renin during the second week was significant in one group of dogs. Noradrenaline at higher rates significantly raised blood pressure and increased plasma concentrations of renin and angiotensin II. Plasma aldosterone concentration did not rise significantly, perhaps because plasma potassium concentration decreased; in support of this theory changes of plasma aldosterone correlated with changes of plasma potassium but not with changes of angiotensin II. The rise in arterial pressure during dose-response studies was related to the increase of plasma noradrenaline. Prolonged infusion of noradrenaline did not alter the dose-response relation between plasma noradrenaline concentration and arterial pressure.
Asunto(s)
Aldosterona/sangre , Angiotensina II/sangre , Presión Sanguínea/efectos de los fármacos , Norepinefrina/farmacología , Potasio/sangre , Renina/sangre , Animales , Perros , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/efectos de los fármacos , Hematócrito , Infusiones Parenterales , Masculino , Norepinefrina/administración & dosificación , Norepinefrina/sangreRESUMEN
The whole body content of sodium, potassium, chlorine, calcium, phosphorus and nitrogen was measured by neutron activation analysis in 13 patients with untreated primary hyperaldosteronism (Conn's syndrome; aldosterone-secreting adenoma). Concurrently, exchangeable sodium and potassium were estimated by isotope dilution. Results were compared with values in the same patients during treatment with potassium-conserving diuretics and again after removal of the adenoma; and also with those in a series of 30 patients having untreated essential hypertension. Both total body and exchangeable sodium were high in Conn's syndrome before treatment and were reduced by spironolactone or amiloride and by subsequent surgery. There was no evidence of alteration in the proportion of non-exchangeable sodium in this disease, in contrast to earlier reports. Total body and exchangeable potassium were low in untreated Conn's syndrome and increased to normal after therapy: the proportion of non-exchangeable potassium was similar before and after treatment, and also similar to that in essential hypertension. Total body chlorine was increased before treatment in Conn's syndrome and returned to normal with therapy; body calcium, phosphorus and nitrogen were normal throughout.
Asunto(s)
Composición Corporal/efectos de los fármacos , Cloro/metabolismo , Hiperaldosteronismo/metabolismo , Potasio/metabolismo , Sodio/metabolismo , Adulto , Anciano , Calcio/metabolismo , Femenino , Humanos , Hiperaldosteronismo/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis de Activación de Neutrones , Nitrógeno/metabolismo , Fósforo/metabolismoRESUMEN
Investigations were performed in 26 patients with essential hypertension and 24 with unilateral renal artery stenosis. In each patient blood was drawn simultaneously and in triplicate, from both renal veins and aorta, for measurement of plasma concentrations of active and inactive renin and of angiotensin II. In 19 patients estimates of individual renal plasma flow were obtained in order to calculate secretion rates for active and inactive renin, and to assess the contribution of renin secretion rate and of renal plasma flow to the renal vein renin ratio. In patients with essential hypertension there was evidence that the kidney secreted active renin (18% mean increase in renal vein concentration above that of arterial plasma; P less than 0.001), but no evidence of secretion of inactive renin (4% mean increase; NS). There was a tendency for the kidney to extract angiotensin II (8% mean decrease in renal vein concentration below that of arterial plasma; P = 0.07). The affected kidney in patients with renal artery stenosis showed marked secretion of active renin (364% mean increase; P less than 0.001) and also secreted inactive renin (80% mean increase; P less than 0.05) with net generation of angiotensin II across the renal circulation (100% mean increase; P less than 0.05). The contralateral kidney exhibited suppressed secretion of active renin (3% mean increase; NS) with no evidence of secretion of inactive renin (2% mean increase; NS), and marked extraction of angiotensin II (50% mean decrease; P less than 0.001). The correlation between combined secretion rate of active renin by both kidneys and the arterial concentration of active renin in patients with essential and renovascular hypertension taken together was strongly positive (r = 0.82; P less than 0.01). The same correlation for inactive renin was weak (r = 0.32; NS). The correlation between the combined secretion rates of active renin by both kidneys and the circulating plasma concentration of angiotensin II (r = +0.60; P less than 0.05) was both significant and positive. By contrast, the total 'secretion' rate of angiotensin II by both kidneys was inversely related to arterial plasma angiotensin II (r = -0.92; P less than 0.001). This latter relationship suggests an important role for the kidney in clearing angiotensin II from the circulation, this being more marked the higher the arterial angiotensin II concentration.(ABSTRACT TRUNCATED AT 400 WORDS)