F. C. Reubi

Interrelations among blood pressure, blood volume, plasma renin activity and urinary catecholamines in benign essential hypertension☆

Interrelations among blood pressure, circulatory volume, plasma renin activity (PRA) and urinary catecholamine excretion rates were studied in normal subjects and in patients with benign essential hypertension. Mean plasma or blood volumes related to lean body mass, products of blood volume and the logarithm of PRA, and catecholamine excretion rates did not differ significantly between normal and hypertensive subjects. In both normal subjects and hypertensive patients, blood pressure levels correlated positively with the noradrenaline excretion rate (r = 0.40 and 0.36, respectively; p less than 0.025) but not with adrenaline excretion, circulatory volume or the volume-renin product. The logarithm of PRA correlated inversely with mean blood pressure in normal subjects (r = 0.40; p less than 0.001) but not in hypertensive patients; however, there was no convincing evidence for an inappropriate blood pressure-PRA relationship as a prominent feature in the hypertensive patients. PRA did not correlate with blood volume. Patients with low PRA relative to sodium excretion (21 per cent of hypertensive population) were consistently normovolemic, but they tended to be older and excreted less (p less than 0.025) adrenaline than patients with normal or high PRA. The patient subgroup with high PRA relative to sodium excretion (11 per cent of population) was hypovolemic (p less than 0.02); despite this, urinary sodium output was high (172 +/- 64 meq/24 hours). These data reveal no evidence for major roles of PRA, circulatory volume and free peripheral catecholamines in the maintenance of benign essential hypertension. Essential hypertension with low PRA is usually not a hypervolemic state, but it may reflect diminished adrenergic activity, factors associated with aging and effects of a high systemic pressure. High PRA in benign essential hypertension may be at least partly a consequence of hypovolemia resulting from high blood pressure-induced sodium diuresis.

Interrelations between age and plasma renin, aldosterone and cortisol, urinary catecholamines, and the body sodium/volume state in normal man

ZusammenfassungUntersuchungen bei 28 jungen (19–29 Jahre), 16 mittel-alten (32–58 Jahre) und 15 älteren (60–74 Jahre) Normalpersonen zeigten eine mit zunehmendem Alter progressive Abnahme der Plasmareninaktivität und -aldosteronkonzentration sowie eine Zunahme der Noradrenalinexkretionsrate. Mit Ausnahme der im Stehen gemessen Plasmaaldosteronspiegel waren die Korrelationen dieser Parameter mit dem Alter (r≥0,34;p<0.05) sowie die Unterschiede der Mittelwerte zwischen jungen und älteren Personen (p<0,02) signifikant. Die Plasmacortisolkonzentration blieb beim Aufstehen bei jungen und mittel-alten Personen im Mittel unverändert (−10 und −8%), stieg jedoch bei älteren Menschen um 50% an (p<0,02). Der Blutdruck korrelierte (p<0,05) bei Analyse der gesamten Studienpopulation mit dem Alter (r=0,35) und der Noradrenalinexkretionsrate (r=0,34), bei den älteren Personen fand sich auch eine signifikante Beziehung zum Blutvolumen (r=0,68). Austauschbares Körpernatrium, Plasma- und Blutvolumina und Adrenalinexkretionsrate zeigten keine signifikanten altersbezogenen Variationen. Plasmarenin- und -aldosteronspiegel korrelierten weder mit diesen letzteren Parametern noch mit dem Blutdruck. Es wird gefolgert, daß der Einfluß des Alters auf Plasmarenin- und -aldosteronwerte, das freie periphere Noradrenalin und die Stimulierbarkeit von Plasmacortisol durch Orthostase in Betracht gezogen werden sollte, wenn immer diese Faktoren bei Patienten mit arterieller Hypertonie oder anderen klinischen Störungen interpretiert werden müssen. Diese Resultate sind außerdem mit der Möglichkeit vereinbar, daß die altersbezogene Zunahme des Liegendblutdrucks beim normalen Menschen zumindest teilweise auf dem parallelen Anstieg des freien peripheren Noradrenalins beruhen könnte.SummaryInterrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamines, plasma and blood volumes, exchangeable body sodium and blood pressure were studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r≥0.34;p<0.05), with significant differences in mean values between young and elderly subjects (p<0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was not statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly (+50%;p<0.02), but not in young (−10%) or middle-aged (−8%) subjects. Blood pressure correlated with age (r=0.35;p<0.05) or noradrenaline excretion rate (r=0.34) in the entire study population and with blood volume in the elderly (r=0.68), but not in the young or middle-aged study groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Furthermore, these data are consistent with the possibility that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.

Changes in renal function in essential hypertension

Abstract Studies of renal hemodynamics, plasma renin activity (PRA), plasma aldosterone, and water and sodium excretion were performed in 171 patients with essential hypertension and 61 normotensive subjects. The para-amino hippurate clearance (C PAH ) was usually normal or moderately reduced in those with benign hypertension and markedly depressed in those with malignant hypertension. The PAH extraction ratio was normal or slightly reduced in the patients with benign hypertension and moderately impaired in those with low C PAH indicating that a disproportionate decrease in cortical flow occurred only in the latter. The c pah did not correlate Inversely with the mean blood pressure in the patients with benign hypotension. Reexamination of untreated patients after an average of 28 12 months revealed a decrease in renal plasma flow but no further increase in blood pressure. These findings suggest that in uncomplicated hypertension the increase in blood pressure is not caused by renal circulatory disturbances. PRA was unrelated to renal hemodynamics in benign hypertension. In malignant hypertension, it was inversely correlated with the renal plasma flow. Under mild loading with isotonic saline solution, the fractional water excretion correlated with the blood pressure. Sodium excretion was neither related to the blood pressure nor to the estimated peritubular oncotic pressure, but correlated inversely with plasma aldosterone. These observations provide no support for the causative role of a primary disturbance in sodium excretion in essential hypertension.

Curable Hypertension with Unilateral Hydronephrosis: Studies on the Role of Circulating Renin

Among eight patients with unilateral hydronephrosis and hypertension, peripheral plasma renin activity was normal in seven and borderline high in one. Four patients had hydronephrotic/contralateral kidney renin ratios of greater than 1.5, suggesting excessive renin release from the diseased kidney, and ratios between contralateral kidney and peripheral blood of less than 1.2, indicating suppressed renin production in the contralateral kidney. Nephrectomy normalized blood pressure in each of these patients. Two patients had hydronephrotic/contralateral kidney renin ratios of less than or equal to 1.3 or contralateral kidney/periphery ratios of greater than 1.2, suggesting ischemia of the contralateral kidney; pyeloplasty or nephrectomy, or both, failed to improve the hypertension. Postoperative changes in blood pressure correlated with changes in peripheral renin (r = 0.90; P less than 0.01). These data suggest that hypertension associated with unilateral hydronephrosis is partly renin-dependent; and renal vein renin values are helpful in selecting patients for surgery.

Alpha and beta adrenergic blockade with orally administered labetalol in hypertension. Studies on blood volume, plasma renin and aldosterone and catecholamine excretion.

Abstract Patients with essential hypertension were treated for 6 weeks with the alpha and beta adrenoceptor blocking agent labetalol alone (no. = 18) or in combination with the diuretic agent chlorthalidone (no. = 11). Maximal doses of labetalol during these trials averaged 1,460 and 650 mg/day, respectively. Significant ( P P P P

Vergleichende Studien zwischen den renalen Clearances von Na-Cr2Cr51-äthylendiamintetraacetat, Inulin und Natriumthiosulfat beim Menschen

ZusammenfassungUnter Standard-Clearance-Bedingungen wurde bei 47 Patienten die Clearance von Cr51-EDTA und Natriumthiosulfat, sowie bei 79 Patienten die Clearance von Cr51-EDTA und diejenige von Inulin miteinander verglichen. Unter den Exploranden in beiden Gruppen befanden sich solche mit normaler Nierenfunktion und solche mit einer Nierenfunktionseinschränkung verschiedenen Ausmaßes. Inulin wurde simultan sowohl mit der Resorcinol-Methode nachSchreiner und der vonSackner undDavidson modifizierten Anthron-Methode bestimmt. In beiden Gruppen ließ sich eine sehr gute Korrelation der Cr51-EDTA-Clearance mit derjenigen der Standard-Indicatoren nachweisen. Die Clearance von Cr51-EDTA liegt wenig, aber eindeutig unterhalb derjenigen von Natriumthiosulfat oder Inulin. Dieser Unterschied kann auf Grund unserer eigenen Teilexperimente und den Daten aus der Literatur nicht einwandfrei erklärt werden. Die Regressionskoeffizienten aus der Inulin-Vergleichsreihe und der Natriumthiosulfat-Vergleichsreihe liegen nahe beieinander und sind statistisch nicht signifikant voneinander verschieden. Aus diesem Grund kann aus den 3 Regressionskoeffizienten ein mittlerer Korrekturfaktor von 1,073 ermittelt werden, mit dem die Cr51-EDTA-Clearance multipliziert werden muß, um die tatsächliche glomeruläre Filtration zu errechnen. Die Strahlenbelastung mit der von uns verwendeten Cr51-Dosis ist für den Patienten trivial und für das technische Personal bedeutungslos. Die Hauptvorteile von Cr51-EDTA gegenüber den Standardindikatoren liegt darin, daß diese Substanz billig ist, sich in vivo inert verhält, sehr einfach und mit hoher Präzision bestimmt werden kann.SummaryUnder standard clearance conditions we have compared the clearance of Cr51-EDTA with the clearance of Na-Thiosulfate in 47 patients with normal and impaired renal function and with the inulin clearance in 79 patients. Inulin was determined both by the Recorcinol and the Anthron method. A high degree of correlation was observed for both groups of comparative studies. Our results show that the clearance of Cr51-EDTA is slightly, but definitely lower than the clearance of Na-Thiosulfate or Inulin. The reasons for this difference are poorly understood. As the regression coefficients in the comparative study with Inulin and Na-Thiosulfate are not statistically different from each other, they may be averaged to obtain a correction factor. Radiation dosage to the patient is trivial and of no importance for the technical personal. We conclude that Cr51-EDTA may be used as a substitute for Na-Thiosulfate or Inulin. The clearance of Cr51-EDTA, however, has to be multiplied by 1.073 to obtain the true glomerular filtration rate. The accuracy and ease, with which Cr51-EDTA can be quantitated and the lack of chemical interference (glucose, mannitol, e.g.) are major advantages of Cr51-EDTA.

Cardiovascular and endocrine profile of adrenergic neurone blockade in normal and hypertensive man

Abstract Some cardiovascular and endocrine effects of adrenergic blockade were assessed in six normal subjects, six patients with mild hypertension (diastolic pressure

Effects of chronic alpha and beta adrenoceptor blockade with labetalol on plasma catecholamines and renal function in hypertension

ZusammenfassungBei 18 Patienten mit essentieller Hypertonie wurde der Einfluß einer chronischen Alpha-und Betarezeptoren-Blockade mit Labetalol auf Plasmakatecholamine und Nierenfunktion untersucht. Plasmanoradrenalin und Adrenalin veränderten sich nach 6wöchiger Behandlung nicht signifikant, während die glomeruläre Filtrationsrate und der renale Plasmafluß um ungefähr 20% abnahmen (P<0,025). Die tubuläre Rejektionsfraktion von Natrium nahm um 36% zu (P<0.001), bei unveränderter Natrium-Ausscheidung im 24 h-Urin. Der geringgradige Abfall der glomerulären Filtrationsrate und des renalen Plasmaflusses scheint nur von geringer klinischer Bedeutung zu sein. Der fehlende Anstieg der Plasmakatecholamine unter der chronischen Alpha-und Betarezeptoren-Blockade mit Labetalol ist vereinbar mit einer selektiven postsynaptischen alpha-blockierenden Wirkung, während die präsynaptische Feedbackkontrolle der Katecholaminausschüttung unbeeinflußt bleibt. Zudem scheint die blutdrucksenkende Wirkung von Labetalol von Änderungen der Aktivität des sympathischen Nervensystems weitgehend unabhängig zu sen.SummaryPlasma catecholamines and renal function were evaluated in 18 patients with essential hypertension treated with the alpha and beta adrenoceptor blocking agent, labetalol. Following 6 weeks of labetalol therapy, blood levels of epinephrine and norepinephrine remained unaltered. Glomerular filtration rate and renal plasma flow were decreased similarly by about 20% (P<0.025). Tubular rejection fraction of sodium was increased by 36% (P<0.001) while sodium excretion was comparable to control conditions. Labetalols potential to cause a mild reduction in kidney function should be considered, but may have no clinical consequences in most hypertensive patients receiving such treatment. The lack of increased plasma catecholamine levels during therapy supports the concept that labetalols alpha-blocking potential is limited to post-junctional receptors, leaving the prejunctional feedback control of catecholamine release intact. Moreover, labetalols blood pressure-lowering mechanism may be largely independent of changes in sympathetic nervous activity.

Acute changes in renal function induced by bisoprolol, a new cardioselective beta-blocking agent

SummaryThe acute effects of bisoprolol 10 mg i.v., a new beta1-selective adrenoceptor antagonist, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), para-aminohippuric acid clearance (CPAH), sodium clearance, urine volume and plasma renin activity (PRA), were studied in 6 patients with essential hypertension. Heart rate decreased by 23%, mBP remained unchanged, and GFR decreased by 14% and CPAH by 23%. PRA was depressed on average by 25%. Urine volume and sodium clearance also declined by 9 and 13%, respectively, but the changes were not statistically significant. The fall in heart rate was significantly correlated with that in GFR and CPAH. Changes in GFR were correlated significantly with those in CPAH. The acute changes in renal function induced by bisoprolol are considered to be due to a reduction in cardiac output and increased systemic vascular resistance.

Hypoaldosteronism without hyperkalemia

ZusammenfassungDer selektive Hypoaldosteronismus ist bisher fast ausschließlich mit Hyperkaliämie als Hauptmanifestation beschrieben worden. Bei 100 Patienten mit Diabetes mellitus und 46 Nierenkranken wurden prospektiv die Häufigkeit von Hypoaldosteronismus und dessen Beziehung zu Plasma-Kalium,-Natrium und -Reninaktivität, Körper-Natrium-Volumenstatus und Nierenfunktion untersucht. 90 Normalpersonen waren die Kontrollen und lieferten die Normbereiche für Plasma-Renin und -Aldosteron in Beziehung zum Alter und/oder Urinnatrium. 6 Diabetiker (6%) und 2 Nierenkranke (4,5%) hatten einen Hypoaldosteronismus; ihr Plasmakreatinin war normal (<1,4 mg/100 ml). 19 Diabetiker (19%) und 13 Nierenkranke (26%) hatten einen grenzwertigen Hypoaldosteronismus; 10 der Nierenkranken hatten ein erhöhtes Plasma-Kreatinin (1,4–3,9 mg/100 ml). Plasma-Cortisol war immer normal. Außer einer Hyperkaliämie bei einem Patienten mit grenzwertigem Hypoaldosteronismus und Azotämie war das Plasmakalium ebenfalls normal. Mittleres Alter, Blutdruck, Plasma-Cortisol und -Elektrolyte, Urin-Kalium, Blutzucker (nur Diabetiker), Blutvolumen, und austauschbares Natrium waren bei Diabetikern oder Nierenkranken mit tiefem, normalem oder hohem Plasmaaldosteron vergleichbar. Plasma-Aldosteron korrelierte (P<0,01) mit Plasma-Renin. Hypoaldosteronismus war mit einer Tendenz zu niedrigem Plasma-Renin assoziiert. Gewisse Patienten mit Hypoaldosteronismus und die meisten mit grenzwertigem Hypoaldosteronismus hatten jedoch normale Reninwerte. Diese Befunde belegen das Vorkommen von Hypoaldosteronismus ohne Hyperkaliämie oder manifestem, renalem Natriumverlust bei Patienten mit nichtazotämischen Diabetes oder Nierenkrankheit. Diese Konstellation spricht dafür, daß Aldosteron als protektiver Faktor gegen Kaliumretention beim nichtazotämischen Menschen eine fakultative Rolle spielt. Asymptomatischer Hypoaldosteronismus ist vermutlich häufiger als die symptomatische Form. Als Ursache kommen Reninmangel oder eine gestörte Nebennierenrindenfunktion in Frage.SummarySelective hypoaldosteronism has almost invariably been described with hyperkalemia as principal manifestation. The prevalence of hypoaldosteronism and its relationship to plasma potassium, sodium, renin activity (PRA), body sodium-volume state and renal function was evaluated prospectively in 100 non-azotemic patients with diabetes mellitus and 46 with renal disease and normal to moderately impaired kidney function. Ninety healthy subjects served as controls and provided normal ranges for PRA and aldosterone (PA) relative to age and/or sodium excretion. Six diabetics (6%) and 2 renal patients (4.5%) had hypoaldosteronism; their plasma creatinine was <1.4 mg/100 ml. Nineteen diabetics (19%) and 13 renal patients (26%) had borderline hypoaldosteronism; 10 of the renal group had a plasma creatinine of 1.4 to 3.9 mg/100 ml. Plasma cortisol was consistently normal. Except for the presence of hyperkalemia in one patient with borderline hypoaldosteronism and azotemia, plasma potassium was also normal. Mean age, blood pressure, plasma cortisol and electrolytes, urinary potassium, blood glucose (diabetics only) and blood volume, exchangeable sodium and renal function were comparable between low, borderline-low or normal PA subgroups with diabetes or kidney disease. The body sodium-volume state was normal except for increased (p<0.01) exchangeable sodium in diabetics. PA correlated (p<0,01) with PRA. Mean PRA tended to be lowered in hypoaldosteronism; but some patients of this subgroup and most with borderline hypoaldosteronism had normal PRA. These findings demonstrate that hypoaldosteronism may exist without hyperkalemia or overt sodium wasting and may accompany non-azotemic diabetes mellitus or renal disease. This constellation favors a more facultative role of aldosterone as factor protecting against potassium retention in non-azotemic man. Asymptomatic hypoaldosteronism is probably more common than the symptomatic form and may be caused by angiotensin-deficiency or altered adrenal function.