[Aldosterone and renin in liver cirrhosis with ascites]. / Adosteron und Renin bei Leberzirrhose mit Aszites.

Supine plasma aldosterone and plasma renin activity were determined in patients with cirrhosis of the liver and ascites (n = 10). Most of the patients initially showed an increase in plasma aldosterone and plasma renin activity. However, values within the normal range were observed (plasma aldosterone, n = 3; plasma renin activity, n = 4). In the ascitic fluid renin activity could not be detected, whereas aldosterone concentrations correlated significantly with the respective plasma levels (r = 0.8, p less than 0.01). During therapy with spironolactone alone (n =2) or in combination with furosemide (n = 4), diuresis and natriuresis showed no correlation with changes in plasma aldosterone and/or plasma renin activity. Our results suggest that other factors than renin and aldosterone secretion may be important in the formation of ascites in patients with cirrhosis of the liver. In addition, the inverse correlation between mean arterial blood pressure and plasma renin activity (r = -0.65, p less than 0.05) found in our patients supports the assumption that the increase in renin secretion is probably induced by changes in (renal) hemodynamics.

[Studies on the differential determination of renin activity in renal venous blood in renal artery stenosis]. / Untersuchungen zur seitengetrennten Bestimmung der Reninaktivität im Nierenvenenblut bei Nierenarterienstenose.

Plasma renin activity (PRA) was determined in both renal veins of 37 patients with angiographically proven renal artery stenosis. Renal venous PRA was determined in 17 patients without furosemide stimulation and in 20 patients before and 15 and 30 min after intravenous injection of 40 mg furosemide. 21 of 37 patients showed abnormally high peripheral PRA. In the 17 patients in whom renal venous PRA was measured without stimulation, 11 showed a PRA ratio (PRA stenotic side/PRA unaffected side) greater than or equal to 1.5. The 20 patients in whom stimulation with furosemide was performed were divided into 2 groups each containing 10 patients: The first group was characterized by an increase in PRA ratio after furosemide stimulation, while in the second group this PRA ratio decreased. In the first group mean duration of hypertension was 4.5 years compared to 7.5 years in the second group. In 17 of 37 patients renal artery stenosis was corrected by surgery. After operation 12 patients became normotensive and in 2 patients hypertension improved. There was no effect of renovascular surgery on blood pressure in only 3 patients. None of these patients showed an increasing ratio in response to furosemide. Our results suggest that the validity of renal venous PRA measurements is enhanced when the procedure is performed before and after administration of furosemide.

[Effect of the angiotensin antagonist saralasin on blood pressure and hemodynamics in patients with terminal renal insufficiency]. / Der Einfluss des Angiotensin-Antagonisten Saralasin auf Blutdruck und Hämodynamik bei Patienten mit terminaler Nieren-insuffizienz

The angiotensin antagonist saralasin was infused both before and 10 hrs after dialysis in 10 hypertensive and 4 normotensive patients hemodialyzed for terminal renal failure. A significant increase in mean arterial pressure (MAP) and total peripheral resistance (TPR) without change in cardiac output measured by impedance cardiography were observed during the first few minutes of saralasin infusion. MAP and TPR decreased during the second half of the infusion in 4 hypertensive patients and remained at the preinfusion levels in 6 hypertensive and 4 normotensive patients. Plasma renin activity (PRA) was significantly higher in patients in whom MAP fell both before and after hemodialysis. There was a significant correlation between PRA before saralasin and the fall in MAP and TPR. The fall in MAP in 4 of 10 hypertensive patients demonstrates that inappropriately high renin and angiotensin levels are involved in the pathogenesis of hypertension in some patients with terminal renal failure. Volume factors are probably of primary importance in the other patients.

[Primary and secondary hypertension in polyclinical patients]. / Primäre und sekundäre Hypertonie in einem poliklinischen Patientengut

Hypertension was found in 854 (10.4%) of 8228 patients (3657 females, 4571 males) seen in our outpatient clinic during 1975. Essential (primary) hypertension was found in 92.9% (n = 793) of all hypertensives. Among secondary forms of hypertension (7.1%) renal hypertension, with a rate of 5.8%, was the commonest form (hypertension of renal-parenchymatous origin 4.9%, renovascular hypertension 0.8%, hypertension associated with unilateral hydronephrosis 0.1%. In 2 patients (0.2%) the underlying disease was primary aldosteronism and in 5 (0.6%) coarctation of the aorta. In 4 female patients (0.5%) the hypertension was caused by oral contraceptives. Patients with essential hypertension had higher body weight than those with normal blood pressure. These differences were statistically significant in young and middle-aged patients. Our results show a very high percentage of essential hypertension. In only 18 (2.1%) of 854 hypertensives was a curable form of high blood pressure found (hypertension caused by renal artery stenosis, hydronephrosis, aldosterone producing adenoma of the adrenal gland and oral contraceptives). The very low percentage of curable forms of hypertension should be kept in mind when deciding on expensive procedures in a search for secondary forms of high blood pressure.

PIP: In a Zurich outpatient clinic in 1975 hypertension was found in 10.4% of 8228 patients (3657 females and 4571 males). Essential (primary) hypertension was found in 92.9% of all hypertensives. Among secondary forms of hypertension (7.1%) renal hypertension was the most common (5.8%) with 4.9% for hypertension of renal parenchymatous origin, .8% renovascular hypertension, and .1% hypertension associated with unilateral hydronephrosis. In 2 patients (.2%) the underlying disease was primary aldosteronism and in 5 (.6%) coarctation of the aorta. In 4 females (.5%) hypertension was caused by oral contraceptives. Patients with essential hypertension had higher body weight than those with normal blood pressure. These differences were statistically significant in young and middle-aged patients. The percentage of primary hypertension was significantly high. In only 18 (2.1%) of 854 hypertensives was a curable form of high blood pressure found (hypertension caused by renal artery stenosis, hydronephrosis, aldosterone-producing adenoma of the adrenal gland, and oral contraceptives). The very low percentage of curable forms of high blood pressure should be kept in mind when deciding on expensive procedures in a search for secondary forms of high blood pressure.

Short-term fluctuations in plasma cortisol in Cushing's syndrome.

Short-term fluctuations in plasma cortisol were determined overnight in twelve patients with Cushing's syndrome: eight patients with bilateral adrenal hyperplasia of hypothalamic-pituitary orgin, three patients with a cortisol producing adenoma and one patient with a carcinoma of the adrenal cortex. While either secretory episodes in plasma cortisol or a fixed pattern of cortisol secretion were observed both in patients with pituitary dependent and in those with pituitary independent hypercorticism, a typical night-day variation in plasma cortisol was only found in one of the eight patients with Cushing's syndrome of hypothalamic-pituitary origin. The patient with a cortisol producing carcinoma showed only minor fluctuations in plasma cortisol throughout the test period. The results indicate that no discrimination can be made between patients with pituitary dependent or independent Cushing's syndrome by demonstrating an episodic or a fixed secretion of cortisol. It seems, however, that the finding of a typical night-day variation in hormone secretion points to hypercorticism of hypothalamic-pituitary orgin.

Control of plasma aldosterone during hemodialysis in patients with terminal renal failure.

The control of plasma aldosterone during hemodialysis was investigated in 31 patients with terminal renal failure. While before hemodialysis renin predominantly influenced aldosterone, this effect dissipated during hemodialysis. In addition, no relationship was observed between changes in aldosterone and those in sodium, potassium and plasma cortisol. In a group of 10 patients isokalemic and isonatremic hemodialysis failed to document an effect sodium or potassium on hemodialysis induced changes in aldosterone. Our data suggest that none of the four factors - renin, ACTH, sodium and potassium - had constantly caused the observed changes in aldosterone during hemodialysis.

Studies on the effect of angiotensin II and of Des -angiotensin II on blood pressure, plasma renin activity and plasma aldosterone in the dog.

1. The effect of infusions of equimolar doses of angiotensin II (AII) and of Des -angiotensin II (heptapeptide) on plasma renin activity, blood pressure and plasma aldosterone were compared in normal anaesthetized dexamethasone-suppressed dogs. 2. Plasma renin activity was equally suppressed by both compounds. The increase in blood pressure induced by the heptapeptide averaged 43-62% of the increase during AII infusions. No significant differences in aldosterone increase were observed between AII and the heptapeptide. Plasma aldosterone, however, dropped significantly faster in heptapeptide-treated dogs after the end of the infusions. 3. Sar -Ala -angiotensin II (saralasin, 400 pmol min-1 kg-1) suppressed plasma aldosterone that was stimulated by heptapeptide (20 pmol min-1 kg-1) completely. The same angiotensin antagonist had only a moderate effect on plasma aldosterone stimulated by AII. After stopping the antagonist infusion, plasma aldosterone rose significantly higher in dogs infused with AII than in those receiving the heptapeptide. 4. The results demonstrate differences between the effects of AII and the heptapeptide both on blood pressure and on plasma aldosterone. They do not support the hypothesis that the heptapeptide may be the main mediator of aldosterone secretion.

[Effect of the angiotensin antagonist saralasin (1-sar-8-ala-angiotensin II) on the blood pressure in secondary hypertension]. / Einfluss des Angiotensin-Antagonisten Saralasin (1-Sar-8-Ala-Angiotensin II) auf den Blutdruck bei sekundärer Hypertonie

The angiotensin antagonist saralasin (1-sar-8-ala-angiotensin II) was given to 27 patients with different forms of secondary hypertension. The blood pressure fell in 6 of 7 patients with renal artery stenosis and in 4 of 10 patients with terminal renal failure on regular hemodialysis. No change or a rise in blood pressure was observed in 3 patients with Cushing's syndrome, 4 patients with primary aldosteronism, 3 patients with hypertension and a unilateral small kidney of other than renovascular origin, and 6 patients with terminal renal failure. It can be concluded from the results that angiotensin II is involved in the pathogenesis of renovascular hypertension and in some cases of hypertension accompanying chronic renal failure.

Control of plasma aldosterone in terminal renal failure before and after nephrectomy and after renal transplantation.

In two patients with terminal renal failure the night-day rhythm of plasma aldosterone (PA) renin activity (PRA) and plasma cortisol (PC) were examined before and after bilateral nephrectomy and after renal transplantation. Before nephrectomy changes in abnormally high PA coincided with PC whereas no significant correlation was observed between PA and PRA. In the anephric state secretory episodes of PA occurred independent from those of PC while PRA was undetectable. After renal transplantation a lack of night-day variation in renin secretion was observed in both patients; only one of the two patients showed episodic secretion of PA while PC was suppressed in both patients probably due to the chronic administration of prednisone. Our results indicate, that before nephrectomy under the conditions described in this study plasma aldosterone was predominantly controlled by ACTH. In the anephric state and after renal transplantation other (yet unidentified) factors might have caused episodic secretion of aldosterone. Finally, the lack of night-day variation and secretory episodes in renin secretion after transplantation points to an important role of the sympathetic nervous system in the control of circadian and episodic renal renin release.

[Transitory remission of hypercorticism by means of cyproheptadine in a patient with Cushing syndrome]. / Nicht dauerhaft Remission des Hyperkortizismus durch Cyproheptadin bei einer Patientin mit Cushing-Syndrom

In patients with Cushing's syndrome of hypothalamischem Cushing-Syndrom wereden eine zentrale Störung und eine wichtige Rolle des Serotonins. Accordingly, in the present study a patient with hypothalamic-pituitary hypercorticism was treated with the seotonin antagonist cyproheptadine. Urinary free cortisol excretion was measured repeatedly before, during and after therapy. In addition, night-day rhythm of plasma cortisol was determined before and at the end of cyproheptadine medication. Within 2 months, therapy with 24 mg cyproheptadine resulted in a lowering of urinary cortisol excretion to normal values. Then, however, despite continuation of the therapy, urinary free cortisol excretion rates again rose to pathological levels. Due to the occurrence of severe psychosis, the drug had to be withdrawn. Before and under cyproheptadine no night-day rhythm of plasma cortisol could be observed.

The effect of saralasin (1sar-8-ala-angiotensin II) on blood pressure in patients with Cushing's syndrome.

To investigate the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome two patients with hypercorticism were infused with 20 mg saralasin (1-sar-8-ala-angiotensin II) over a period of 30 minutes under constant blood pressue control. In addition, one patient with primary aldosteronism, an established form of mineralocorticoid hypertension, served as control. Neither in the two patients with Cushing's syndrome nor in the patient with primary aldosteronism could a blood pressure lowering effect of saralasin be observed. In the two patients with hypercoritcism both renin activity and plasma aldosterone increased during saralasin infusion. The patient with primary aldosteronism only showed a weak increase in plasma aldosterone concentration.

[Blood pressure and renin activity in essential hypertension under pindolol]. / Blutdruck und Reninaktivität bei essentieller Hypertonie unter Pindolol

20 essential hypertension patients with diastolic blood pressure of 100-140 mm Hg were treated with increasing doses (15-45 mg/day by mouth) of pindolol for 14 weeks after an initial placebo period of 5 weeks. Systolic and diastolic blood pressure decreased significantly with as little as 15 mg of pindolol (p less than 0.001). No further changes in systolic and diastolic blood pressure were observed when the doses of pindolol were increased. Plasma renin activity (PRA) determined by radioimmunoassay did not change under increasing doses of pindolol. The blood pressure changes did not correlate with initial PRA or with individual changes in PRA under increasing doses with individual changes in PRA under increasing doses of pindolol. These results do not afford evidence for a renin-dependent hypotensive effect of pindolol.

[The value of renin determination in the diagnosis of hypertension]. / Die Bedeutung der Reninbestimmung bei der Hypertonie-Abklärung

Primary aldosteronism and renovascular hypertension are two different diseases in which renin determinations are necessary for establishment of diagnosis or therapeutic procedure. Low renin values which are not stimulated by acute stimuli combined with elevated plasma aldosterone concentrations confirm the diagnosis of primary aldosteronism. When in a patient with proven renal artery stenosis a significant difference in renal venous renin activity is observed between the two kidneys, a connection between hypertension and renal artery stenosis is likely when in addition the renin secretion of the unaffected kidney is suppressed. A favourable outcome for surgery can be predicted when the individual clinical picture in such a case is also considered. A similar view also holds for the connection between hypertension and unilateral small kidney not due to renal artery stenosis. In essential hypertension the plasma renin level makes it possible to a certain extent to predict whether a patient will benefit from diuretics or from beta-blocking agents. Despite this experience, however, renin determinations are not indicated in every case of essential hypertension. It has not been proven that the prognosis of this disease is improved by renin oriented monotherapy rather than by effective treatment with other antihypertensive agents.

[Primary aldosteronism]. / Primärer Aldosteronismus

The syndrome of primary aldosteronism is caused either by an aldosterone-producing adenoma or by idiopathic bilateral adrenal hyperplasia. Hypokalemic hypertension is the leading symptome of the disease. Diagnosis is by the combination of abnormally high and non-suppressible aldosterone values with undetectable or low renin values unresponsive to postural changes or salt restriction. Patients with aldosterone-producing adenoma normally show a fall in plasma aldosterone in response to posture and ACTH-dependent circadian rhythm of aldosterone, whereas bilateral hyperplasia is characterized by postural increases in plasma aldosterone and an ACTH-independent diurnal aldosterone rhythm. These creteria serve to differentiate between adenoma and hyperplasia. An aldosterone-producing adenoma can be localized by veinography, determination of aldosterone concentration in both adrenal veins and by 131I-cholesterol scintigraphy. In our hands the determination of aldosterone in blood from both adrenal veins is the most efficient procedure. In interpreting the results, however, rhythmic and sudden changes in adrenal hormone secretion should be considered. In cases where no adrenal venous blood is obtained, 131I-cholesterol scintigraphy may be used to localize adenoma. In patients with aldosterone-producing adenomas unilateral adrenalectomy should be performed, whereas patients with idiopathic bilateral hyperplasia should receive antihypertensive therapy. As rare instances of primary aldosteronism, a case of aldosterone-producing carcinoma of the adrenal cortex and a case of presumably unilateral adrenal hyperplasia are reported.

[Effect of saralasin on normal blood pressure and on reno-vascular hypertension (author's transl)]. / Angiotensinblockade mit Saralasin. Einfluss auf den normalen Blutdruck und auf den renovaskulären Hochdruck

The angiotensin antagonist saralasin was given intravenously to six normotensive students before and after dietary sodium restriction and to two patients with renovascular hypertension. Both patients responded to the angiotensin antagonist with a decrease of the systolic (32 and 38 mm Hg) and of the diastolic (29 and 16 mm Hg) blood pressure. The small changes in blood pressure observed in the normotensive subjects during the infusion of the angiotensin antagonist indicate that angiotensin II plays no important role in the control of normal blood pressure in recumbent men. The fall in blood pressure induced by saralasin in both patients, however, demonstrates that their hypertension was at least partly angiotensin-dependent. Renal vein renin determination led to the same conclusions. The saralasin infusion test seems to be a simple procedure to diagnose angiotensin-dependent hypertension and will probably help to identify patients with suspected renovascular hypertension.