RESUMO
A simplified radioimmunoassay of urinary aldosterone is reported. Acid-hydrolyzed urine was extracted with dichloromethane and the extract assayed without further purification, Urinary aldosterone values in patients with Cushing's syndrome, low and normal-renin essential hypertension, congenital adrenal hyperplasia, and primary aldosteronism determined by this method agreed closely (r = 0.95, P less than 0.01) with values obtained using a standardized chromatographic method. This simplified assay represents a significant advance in out capabilitites for evaluating patients for abnormalities in aldosterone physiology.
Assuntos
Aldosterona/urina , Radioimunoensaio/métodos , Doenças das Glândulas Suprarrenais/urina , Cromatografia em Papel , Síndrome de Cushing/urina , Humanos , Hiperaldosteronismo/urina , Hiperplasia/urina , Hipertensão/urinaRESUMO
Nadolol was effective and well tolerated as once-daily monotherapy for mild to moderate essential supine diastolic hypertension (SDBP) in 10 young (mean age, 39 years) and 12 elderly (mean age, 68 years) patients in a single-blind, placebo-baseline, escalating-dose study. Doses required to reduce SDBP to 90 mm Hg were not different in young (1.08 +/- 0.21 mg/kg/day) and elderly (0.82 +/- 0.14 mg/kg/day) patients (mean +/- SE). Trough plasma nadolol concentrations at steady state were similar and were linearly related to dose in both groups. More unchanged nadolol was recovered in 24-hour urine samples from young subjects (15.6% +/- 1.9%) than from elderly ones (10.7% +/- 1.1%) (p = 0.028). With increasing nadolol doses, plasma norepinephrine concentration increased and isoproterenol sensitivity decreased in both young and elderly subjects, and creatinine clearance and plasma active renin levels were unchanged; plasma inactive renin levels increased in the young, and aldosterone concentration declined in the elderly with the lowest nadolol dose.
Assuntos
Envelhecimento/metabolismo , Hipertensão/tratamento farmacológico , Nadolol/farmacologia , Adulto , Idoso , Aldosterona/sangue , Creatinina/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nadolol/administração & dosagem , Nadolol/farmacocinética , Norepinefrina/sangue , Renina/sangueRESUMO
We studied the short-term effect of oral doses of quinine and quinidine on the renal clearance of amantadine in healthy young (age range, 27 to 39 years) and older (age range, 60 to 72 years) adults of both genders in a three-limbed randomized crossover study. Renal clearance of amantadine (13.2 +/- 5.8 L/hr) was significantly inhibited by quinine (9.7 +/- 4.8 L/hr) and quinidine (8.9 +/- 4.0 L/hr) only in male subjects and was not associated with age. The chiral selectivity for the renal clearance of quinidine over quinine was confirmed and extended with the suggestion of both age- and gender-associated changes on the renal clearance ratio for these two diastereomeric drugs. These data support the continued use of amantadine for studies on the renal elimination of organic cationic drugs.
Assuntos
Amantadina/farmacocinética , Rim/efeitos dos fármacos , Quinidina/farmacologia , Quinina/farmacologia , Adulto , Idoso , Envelhecimento/metabolismo , Análise de Variância , Interações Medicamentosas , Feminino , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Valores de Referência , Caracteres SexuaisRESUMO
Active and inactive renin have been studied in peritoneal fluid and plasma of six patients with ascites and four patients on peritoneal dialysis (using concentrated dialysate). Acid-pepsin and trypsin activation gave similar results. In ascitic patients mean (+/- s.e.) plasma active renin was very high (0.31 +/- 0.99 pmol angiotensin l/l/s) compared with normal subjects (0.31 +/- 0.08 pmol ANG l/l/s). Plasma inactive renin (1.27 +/- 0.30 pmol ANG l/l/s) was similar to normal subjects (1.31 +/- 0.31 pmol ANG l/l/s) while the mean percentage of total renin which was inactive was 29.7 and 76.5. In ascitic fluid, active renin was very low (0.36 +/- 0.09 pmol ANG l/l/s) but inactive renin (2.15 +/- 0.28 pmol ANG l/l/s) was higher than plasma. Percentage of total renin inactive was 85.8. Peritoneal dialysate showed even smaller amounts of active renin but similar inactive renin with 95.4 per cent inactive (versus 73.8 in their plasma). Peritoneal fluid inactive renin was similar to that in plasma by affigel chromatography and gel filtration and showed, after activation, similar pH optima and Michaelis constants to plasma and peritoneal active renin.
Assuntos
Líquido Ascítico/metabolismo , Diálise Peritoneal , Renina/metabolismo , Transporte Biológico , Cromatografia de Afinidade , Cromatografia em Gel , Humanos , Peso Molecular , Radioimunoensaio , Renina/antagonistas & inibidores , Renina/sangueRESUMO
This study was designed to determine the extent to which differences in criteria for dialysis patient selection and availability of financial resources cause the wide variation in acceptance rates for dialysis in Canada, the United Kingdom, and the United States. We also sought to determine whether there is agreement among nephrologists in the three countries on which patients should not be offered dialysis. We used a cross-sectional survey of all members of the Canadian Society of Nephrology and the Renal Association of Great Britain, and a randomized sample of 800 members of the American Society of Nephrology. Five case vignettes were presented asking for yes/no decisions on offering or not offering dialysis, together with ranking of factors considered important. We also inquired about dialysis resources and physician demographics. We compared responses by country. More nephrologists from the United Kingdom returned responses (83%) than Canadian (53%) or American (36%) nephrologists. American nephrologists offered dialysis more than Canadian or British nephrologists (three of five cases; P < 0.04 to P < 0.001) and ranked patient/family wishes (three of five cases; P < 0.057 to P < 0.0001) and fear of lawsuit (P < 0.04 to P = 0.0012) higher than British or Canadian nephrologists. Canadian and British nephrologists reported their perception of patients' quality of life as a reason to provide (P = 0.0019) or not provide (P = 0.068 to P = 0.0026) dialysis more often than their American counterparts. Despite these differences, nephrologists from each country did not differ by more than 30% on any decision and ranked factors almost identically. Ten percent and 12% of Canadian and British nephrologists, respectively, but only 2% of American nephrologists, reported refusing dialysis due to lack of resources (P < 0.0001). We conclude that the wide variation in dialysis acceptance rates in the three countries is somewhat influenced by differences in patient selection criteria and withholding of dialysis by nephrologists based on financial constraints, but that other factors, such as differences in rates of patient nonreferral for dialysis, contribute more significantly to the variation. Generally agreed on practice guidelines for dialysis patient selection appear possible.
Assuntos
Alocação de Recursos para a Atenção à Saúde , Internacionalidade , Falência Renal Crônica/terapia , Seleção de Pacientes , Diálise Renal , Alocação de Recursos , Adulto , Idoso , Atitude do Pessoal de Saúde , Canadá , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Medicare , Padrões de Prática Médica/estatística & dados numéricos , Qualidade de Vida , Diálise Renal/economia , Diálise Renal/estatística & dados numéricos , Reino Unido , Estados Unidos , Suspensão de TratamentoRESUMO
We studied changes in the peripheral plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in seven patients with congestive heart failure (CHF) during four 1-h protocols during which patients maintained either an upright or a supine posture with or without nasal continuous positive airway pressure therapy (N-CPAP) at a pressure of 10 cm H2O (FIO2 = 0.21). The mean plasma ANP concentration of patients increased significantly from baseline at the end of 1 h of recumbency (65.9 +/- 5.8 to 82.6 +/- 8.3 pg/mL (mean +/- standard error); p < 0.05). This increase was prevented by concomitant N-CPAP therapy (72.1 +/- 8.0 to 61.0 +/- 8.8 pg/mL; p = NS). The mean level of ANP decreased significantly (71.9 +/- 9.0 to 62.5 +/- 8.0 pg/mL; p < 0.05) while patients simply maintained an upright posture. A significant reduction was also observed when patients remained upright with accompanying N-CPAP (72.6 +/- 10.9 to 54.6 +/- 4.3 pg/mL; p < 0.05). There were no significant changes observed in the mean level of BNP for any of the protocols undertaken. We conclude that in patients with chronic CHF, (1) an increase in ANP concentration occurs with recumbency, and this can be prevented by N-CPAP therapy; (2) a decrease in ANP occurs with maintenance of an upright posture, and that this reduction may be augmented by N-CPAP; and (3) no net change in BNP concentration occurs with either posture change or N-CPAP.
Assuntos
Fator Natriurético Atrial/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Proteínas do Tecido Nervoso/sangue , Respiração com Pressão Positiva , Postura/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético EncefálicoRESUMO
Using flat bed isoelectric focusing, inactive renins from various body fluids were compared. Normal plasma inactive renin demonstrated six consistent peaks at pH 4.98, 5.14, 5.29, 5.47, 5.63 and 5.91, the largest being 5.29, 5.47 and 5.63. The isoelectric pattern of ovarian follicular fluid inactive renin was similar, with slight shifts at major peaks to a higher pH. Pregnancy plasma had inactive renin patterns like normal human plasma as did pleural fluid, lymphocoele fluid and plasma from anephric humans. Amniotic fluid inactive renin showed a markedly different pattern with major peaks at pH 5.00, 5.16 and 5.30. Fetal plasma (cord blood) also showed differences with only four peaks at 5.24, 5.40, 5.58 and 5.83. We conclude that human prorenin isoelectric patterns are similar for plasma, ovarian and most tissue fluid prorenins, but different for fetal plasma and amniotic fluid suggesting that these forms of renin do not cross the placental barrier.
Assuntos
Líquidos Corporais/química , Precursores Enzimáticos/análise , Renina/análise , Líquido Amniótico/química , Precursores Enzimáticos/sangue , Feminino , Sangue Fetal/química , Líquido Folicular/química , Humanos , Focalização Isoelétrica , Gravidez , Renina/sangueRESUMO
A fluorescein-labelled antiserum to human Tamm-Horsfall mucoprotein applied to frozen human kidney sections gave strong specific labelling, mainly of cells of tubules in the outer medulla. By comparison with adjacent serial sections stained for alkaline phosphatase and succinic dehydrogenase, it is suggested that material reacting immunologically as Tamm-Horsfall muco-protein is found particularly in the cells of the ascending limb of the loop of Henle and the macula densa segment of the distal tubule.
Assuntos
Rim/análise , Mucoproteínas/análise , Fosfatase Alcalina/análise , Animais , Imunofluorescência , Histocitoquímica , Humanos , Rim/imunologia , Túbulos Renais/análise , Túbulos Renais/enzimologia , Ovinos , Succinato Desidrogenase/análiseRESUMO
The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (less than 50 years) and old (greater than 65 years) hypertensive patients. Captopril effectively decreased blood pressure in both groups (diastolic blood pressure less than 90 mm Hg), with the young patients requiring a lower dose (.7 mg/kg) than the elderly patients (1.2 mg/kg). Creatinine and para-aminohippurate clearances were maintained in both groups, with a decrease in renal vascular resistance being observed in the younger patients. Serum aldosterone levels fell significantly after each dose of captopril at all phases of the study, with no change observed in plasma renin levels. Atrial natriuretic peptide (ANP) level was increased in the elderly patients receiving placebo (48.8 +/- 8 pg/mL) when compared with the young subjects (24 +/- 3.8 pg/mL). Captopril did not alter ANP levels in either group.
Assuntos
Captopril/uso terapêutico , Hipertensão/tratamento farmacológico , Circulação Renal/efeitos dos fármacos , Adulto , Fatores Etários , Idoso , Inibidores da Enzima Conversora de Angiotensina/sangue , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Captopril/sangue , Avaliação de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Renina/sangue , Fatores de TempoAssuntos
Aldosterona/sangue , Animais , Especificidade de Anticorpos , Reações Cruzadas , Humanos , Hidrocarbonetos Clorados , Metano , Oximas , Coelhos/imunologia , Radioimunoensaio , TrítioAssuntos
Transplante de Rim , Adolescente , Adulto , Transfusão de Sangue , Cadáver , Criança , Pré-Escolar , Ciclosporinas/uso terapêutico , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Manitoba , Pessoa de Meia-Idade , Gravidez , Cuidados Pré-Operatórios , Doadores de TecidosAssuntos
Hialina , Mucoproteínas/urina , Cálculos Urinários/etiologia , Humanos , Microscopia EletrônicaRESUMO
Future hypertension research will include not only fundamental pathophysiology and new methods of drug therapy but also research into which groups require special treatment. Hypertension is most common in the elderly, but after age 70 is only weakly associated with cardiovascular morbidity and mortality, mainly in females, and more related to systolic hypertension than diastolic. Hypotensive therapy has not yet proven to be of benefit in this age group. Trials of therapy, perhaps especially in systolic hypertension, in women and in previous stroke victims could well be carried out cooperatively by family physicians. The effectiveness of salt reduction and weight reduction in lowering blood pressure is controversial, but could be tested in cooperative trials, especially for borderline hypertensives and possibly for children of hypertensive parents.
RESUMO
1. Six essential hypertensive patients (five with low renin) were treated in successive weeks with placebo; hydrochlorothiazide 100 mg (382 micromol)/day; hydrochlorothiazide and 50 mmol of sodium/day diet; hydrochlorothiazide, 50 mmol of sodium diet and propranolol 160 mg (544 micromol)/day; and hydrochlorothiazide, 50 mmol of sodium and indomethacin 100 mg (287 micromol)/day. 2. Although blood pressure remained unchanged and serum potassium fell on diuretic with or without low salt, there was a marked increase of active renin and a lesser increase of inactive renin, resulting in an increased proportion of active to total renin. 3. Propranolol decreased both active and inactive renin, but not significantly. 4. Indomethacin produced a marked suppression of active renin, a smaller reduction in inactive renin, and a reduction of the ratio of active to total renin almost to placebo values. 5. Blood pressure rose to control values on indomethacin despite the fall in renin whereas it fell with propranolol with little change in renin. 6. Serum aldosterone rose with stimulation but remained elevated despite effective renin suppression with indomethacin and continuing reduced serum potassium concentration.
Assuntos
Hidroclorotiazida/farmacologia , Hipertensão/enzimologia , Indometacina/farmacologia , Propranolol/farmacologia , Renina/sangue , Adulto , Aldosterona/sangue , Pressão Sanguínea/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Potássio/sangue , Sódio/sangue , Sódio/urinaRESUMO
1. Rabbit plasma enzymes that degrade angiotensin I are inhibited completely by the combination of 2,3-dimercaptopropan-1-ol (10mm), EDTA (10mm) and chlorhexidine gluconate (0.005%, w/v). These compounds do not modify the reaction of renin with renin substrate and are termed the selective inhibitors. 2. The renin substrate concentration of plasma can be measured as angiotensin I content by incubating plasma plus the selective inhibitors with renin for a time sufficient to allow complete utilization of renin substrate. 3. This reaction obeys first-order kinetics to substrate concentrations of at least 1000ng. of angiotensin I content/ml. In general, the renin substrate concentrations of normal rabbit plasmas are less than 1000ng. of angiotensin I content/ml. Thus the time required for the complete release of angiotensin I from normal plasma is inversely related to renin activity and is independent of renin substrate concentration. 4. A method for the assay of renin substrate, taking these reaction kinetics into account, is presented.
Assuntos
Angiotensina II/análise , Renina/sangue , Álcoois , Animais , Fenômenos Químicos , Química , Cromatografia em Gel , Distribuição Contracorrente , Ácido Edético , Gluconatos , Heparina , Rim/fisiologia , Cinética , Mercúrio , Métodos , Nefrectomia , Coelhos , Renina/antagonistas & inibidoresRESUMO
Several major studies investigated the possibility of a primary preventive effect of beta-blockers. The International Prospective Primary Prevention Study in Hypertension (IPPPSH) compared a beta-blocker-containing vs. a non-beta-blocker-containing antihypertensive regimen in 6,357 moderate-severe hypertensive men and women treated over 3-5 years. Blood pressure (BP) control was comparable with either regimen. beta-Blocker treatment was associated with less hypokalemia, earlier electrocardiogram normalization, and fewer withdrawals for uncontrolled hypertension. In agreement with the Medical Research Council (MRC) trial on mild hypertension and the Heart Attack Primary Prevention in Hypertension (HAPPHY) trial, but at variance with the Primary Prevention Metoprolol in Patients with Hypertension (MAPHY) study, cardiac event rates were similar in beta-blocker- and non-beta-blocker-treated patients. With either regimen, in-study BP reduction was associated with a lower rate of stroke as well as of cardiac events. In a subgroup analysis, nonsmokers appeared to derive beta-blocker benefit, the results being similar to those of the MRC. Smokers required higher doses of drugs to achieve diastolic target pressure, had a higher heart rate and hematocrit, and a higher cardiac event rate than nonsmokers at any given level of diastolic pressure. Except for the MAPHY trial, these primary prevention studies do not support the concept of a cardiac primary preventive effect of antihypertensive beta-blockade but stress the importance of good BP control and a comprehensive risk factor prevention approach in the management of hypertensive patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Fumar/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Morte Súbita , Eletrocardiografia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controleRESUMO
This Symposium includes 15 presentations and an editorial review dealing with prorenin activation and function. It comes 20 years after prorenin was first reported in various contexts and attracted attention because of its connection with renin--angiotensin, its high concentration relative to renin in the blood, and its presence in extrarenal, as well as renal, tissues. Intriguing changes in plasma prorenin have been reported after treatment with antihypertensive and other drugs, following various physiological stimuli, and in pathophysiological states such as Wilms' tumor, Bartter's syndrome, and diabetic nephropathy. Lately, very high prorenin concentrations have been found in human and animal ocular fluid, ovarian follicular fluid, and in association with angiogenesis and microangiopathy. High circulating prorenin concentrations and fulminant hypertension have been reported in rats harbouring the mouse Ren-2 gene. However, what prorenin does in all these extrarenal fluids, tissues, and conditions is not well understood. Among the reasons for this lack of understanding are the difficulties in measuring prorenin and in establishing good animal models. We have not answered the critical question as to whether prorenin itself is bioactive like a hormone, and if so, what its action(s) might be. Nor have we established the main alternative, i.e., whether the function of prorenin is indirect, through renin--angiotensin, be it in the circulation or in the extrarenal tissues. This Symposium provides only partial methodological advances and answers, but we hope it will stimulate the breakthrough work needed to supply more complete answers.
Assuntos
Precursores Enzimáticos/fisiologia , Renina/fisiologia , Ativação Enzimática/fisiologia , Humanos , Sistema Renina-Angiotensina/fisiologiaRESUMO
1. EDTA (10mm), 2,3-dimercaptopropan-1-ol (10mm) and chlorhexidine gluconate (0.005%, w/v) cause complete inactivation of plasma enzymes that degrade angiotensin I, but have no effect on the reaction of renin with its substrate. The reagents were termed the selective inhibitors. 2. Thus it is possible to measure renin in plasma by its ability to catalyse the release of angiotensin I. 3. Sterile plasma, treated with the selective inhibitors, is incubated with renin substrate (500-1000ng. of angiotensin content/ml.) at pH6 at 42 degrees for 6hr. 4. Under these conditions the reaction obeys first-order kinetics. Renin activity is calculated in terms of the percentage release of the angiotensin content/hr. 5. As described, the assay is sufficiently sensitive to measure renin in the plasma of all normal rabbits. By extending the length of the incubation, much lower activities can be measured.
Assuntos
Renina/sangue , Álcoois , Angiotensina II , Animais , Fenômenos Químicos , Química , Distribuição Contracorrente , Ácido Edético , Gluconatos , Concentração de Íons de Hidrogênio , Calicreínas/antagonistas & inibidores , Cinética , Métodos , Coelhos , Renina/antagonistas & inibidores , TemperaturaRESUMO
1 In a placebo-controlled study, the respective anti-hypertensive effects of hydrochlorothiazide and hydrochlorothiazide plus the beta-adrenoceptor blocker acebutolol were assessed in 18 patients with moderately severe essential hypertension. 2 Hydrochlorothiazide 100 mg daily decreased the mean supine blood pressures from 163/107 mmHg to 150/103 mmHg. Addition of acebutolol in a single-blind fashion in doses up to 800 mg daily reduced mean supine pressure to 137/95 mmHg. Further increases in acebutolol dosage to a maximum of 2000 mg daily in 13 patients whose hypertension was not well controlled on lower doses resulted in a mean supine blood pressure of 132/92 mmHg.
Assuntos
Acebutolol/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Acebutolol/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Potássio/sangueRESUMO
Data from 40 patients attending a hypertension clinic staffed by physicians were compared to data from 40 patients attending a hypertension clinic staffed by nurses over a period of 15 months. Nurses appeared to have more success in handling obesity and to achieve somewhat better control of hypertension. Attrition rate was 50 per cent, but particularly high in patients not receiving medication in the physician clinic. There were no differences in appointment keeping.