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Biomedical subjects

G Wambach

Publications and source records attributed to G Wambach.

At least 73 records · Page 4Linked to original sources
PubMed1986

Vasopressor and vasodepressor hormone-systems in adolescent hypertension.

We investigated the activity of the renin-angiotensin-aldosterone-system, the secretion of catecholamines and the kallikrein-kinin-system in 126 adolescents randomly selected from a large study of 1342 young people examined in an epidemiological survey conducted in Cologne in 1975, 1976 and 1980. 73 of them with arterial blood pressures below 145/90 mm Hg were called "normotensives" (systolic blood pressure 127.2 +/- 1.0 mm Hg, diastolic bp 79.7 +/- 0.8 mm Hg). They were compared with 53 "hypertensives" (systolic blood pressure 147.2 +/- 1.6 mm Hg, diastolic bp 93.7 +/- 1.1 mm Hg). Urinary catecholamines were significantly higher in the hypertensives (155.0 +/- 13.3 micrograms/d) compared to the normotensives (100.7 +/- 5.3 micrograms/d) (p less than 0.001) whereas plasma levels of adrenaline and noradrenaline were similar. Serum aldosterone levels and plasma-renin-concentrations were not different between the two groups. Angiotensin-converting-enzyme-activity was slightly higher in the hypertensive group (107.1 +/- 3.5 U/l versus 98.0 +/- 2.6 U/l, p less than 0.001). Urinary kallikrein excretion was found to be modestly lower in hypertensives compared to normotensives (0.40 +/- 0.05 versus 0.55 +/- 0.06 mU/mg creatinine). Urinary excretion of sodium and potassium, blood levels of glucose, uric acid, cholesterol and triglycerides were similar in both groups. The results of the present study suggest an increased sympathetic activity in the early stage of hypertension in adolescents.

Adolescent↗
PubMed1986

Plasma levels of atrial natriuretic peptide (ANP) during mineralocorticoid escape in normal man.

A natriuretic factor has long been postulated to play a role in renal mineralocorticoid escape. We therefore investigated changes in plasma levels of atrial natriuretic peptide (ANP) during chronic treatment with 9 alpha-fluorohydrocortisone. Five normal subjects were studied on a constant diet (300 meq Na+ and 72 meq K+ per day) and received 0.8 mg 9 alpha-fluorohydrocortisone for up to 14 days. Sodium balance became positive and body weight increased between 1.0-4.5 kg maximally. Serum aldosterone was suppressed and plasma levels of ANP were stimulated up to 10-fold. Increment in plasma ANP was positively correlated with the gain in body weight (r = 0.666, p less than 0.001). Renormalization of sodium balance was seen in two subjects, however the maximum in plasma ANP did not occur during the time of renal escape. ANP-secretion is stimulated during sodium retention induced by mineralocorticoids, however ANP does not seem to trigger the escape mechanism.

Adult↗
PubMed1985

Na-K pump activity in erythrocytes of patients with endogenous and exogenous glucocorticoid excess.

The mechanism of glucocorticoid-induced hypertension is not clarified. Recent data suggest an alteration of active electrolyte transport systems by glucocorticoids. We therefore studied the activities of the Na-K pump by measuring the Na-K-ATPase activity in erythrocyte ghosts and the ouabain-sensitive uptake of rubidium in erythrocytes of patients with Cushing's syndrome and of patients with exogenous glucocorticoid excess after treatment with fluocortolone or ACTH. Na-K-ATPase activity was significantly increased in patients with Cushing's syndrome and in patients treated with ACTH compared to the controls. Similarly, total uptake of 86Rb and the ouabain-sensitive uptake in erythrocytes were found to be above the control range both in patients with Cushing's syndrome and in patients treated with fluocortolone. There was no difference in furosemide-sensitive uptake of 86Rb. The results demonstrate an increased maximal activity of the Na-K pump in patients with glucocorticoid excess.

Adrenocorticotropic Hormone↗
PubMed1985

Sodium transport and red cell deformability.

Inhibition of the Na-K pump by a circulating factor is thought to be of importance in the pathophysiology of essential hypertension. We tested the correlation between an inhibition of the Na-K pump by digoxin and the deformability of red blood cells (RBC) both in vitro and in vivo. Erythrocytes were incubated with digoxin (0-1.3 mumol/l) for 1 h at 37 degrees C. Highest concentration of digoxin (0.13 and 1.3 mumol/l) significantly diminished Na-K pump activity, measured by uptake of 86rubidium (Rb). There was a parallel decrease in red cell filtrability. In nine healthy volunteers, intake of digoxin (0.2 mg b.i.d.) over a 5-day period did not alter red cell deformability and uptake of 86Rb. Taken together, inhibition of the Na-K pump in vitro correlates with a reduced red cell deformability. However, this occurs at a toxic dosis of digoxin.

Adult↗
PubMed1985

Haemorheology in adolescent hypertensives.

Fifty-three untreated borderline hypertensives and 73 normotensives were randomly selected from 1342 adolescents (age range 23-27 years) who were examined in 1975, 1976 and 1980 in an epidemiological study. Blood pressure was 127.2 +/- 1.0/79.0 +/- 0.8 mmHg in normotensives and 147.2 +/- 1.6/93.7 +/- 1.1 mmHg in hypertensives (P < 0.001). Erythrocyte deformability was measured with a positive pressure filter system (pore diameter 5 microns) at 37 degrees C. Erythrocyte deformability was significantly increased in hypertensives with a value of 1.77 +/- 0.05, compared with 1.64 +/- 0.04 in normotensives (P < 0.05). No difference in apparent whole blood viscosity, haematocrit and plasma fibrinogen was measurable between the groups. Although plasma noradrenaline and adrenaline concentration at rest and after 3 min standing were not different, excretion of urinary catecholamines was significantly elevated in hypertensives with 155.0 +/- 3.3 micrograms/24 h (normotensives: 100.7 +/- 5.3 micrograms/24 h; P < 0.001).

Adolescent↗
PubMed1984

Cardiovascular and adrenal sensitivity to angiotensin II in essential hypertension.

Regulation of aldosterone secretion by sodium chloride is impaired in a group of essential hypertensives: high-salt diet fails to suppress aldosterone in these patients despite low renin values. The mechanism of this impaired regulation of aldosterone has not been clarified so far. We tested the sensitivity of aldosterone secretion and blood pressure to A II in 20 normotensive controls (aged 20-60, MAP 92 +/- 3 mm Hg), in ten normotensives with one or two parents with hypertension, and in 21 patients with essential hypertension (aged 17-65, MAP 119 +/- 4 mm Hg). After a period of 6 days on high-salt intake (300-320 mEq Na+/day), A II (0.1, 0.5, 1.0 and 2.0 ng/kg/min) was infused, each concentration for 30 min. According to aldosterone excretion during sodium loading, patients were divided into group A with complete suppression (n = 12, aldosterone excretion 3.6 +/- 0.4 microgram/day) and in group B with insufficient suppression (n = 9, aldosterone excretion 15.5 +/- 2.3 micrograms/day). Despite similarly low plasma renins, rise of serum aldosterone levels during A II infusion was significantly higher in group B patients than in group A patients and normotensive controls. Rise in mean arterial blood pressure, however, brought about by graded A II infusion was similar in both groups of hypertensives and in normotensive controls. The results demonstrate an increased adrenal sensitivity to A II in a subgroup of essential hypertensives only. A similar adrenal hypersensitivity to A II found by others in patients with hyperaldosteronism due to adrenal hyperplasia supports the hypothesis that the same mechanism underlies both disorders.

Adolescent↗
PubMed1984

[Recurring thrombosis of the subclavian vein during estrogen therapy of prostatic cancer].

A cardiac pacemaker had been implanted in a patient with carcinoma of the prostate because of a sick sinus node. Thrombosis of the left subclavian vein occurred four weeks later. After complete recanalisation following thrombolytic treatment a recurrence of the thrombosis occurred during high-dosage intravenous oestrogen treatment. Continuous increase of prothrombin time was observed during oestrogen administration while the oral anticoagulation had remained unaltered. This indicated increase of synthesis of vitamin-K-dependent clotting factors by the oestrogens. This case demonstrates that in patients with implanted material and oral long-term anticoagulation the indication for oestrogen treatment must be extremely accurately. In every case very close surveillance of coagulation is necessary.

Blood Coagulation Tests↗
PubMed1984

The renal action of spirorenone and other 6 beta,7 beta; 15 beta,16 beta-dimethylene-17-spirolactones, a new type of steroidal aldosterone antagonists.

The aldosterone antagonistic activity in vivo and the affinity for mineralocorticoid receptors (MCR) in vitro of 3-(17 beta-hydroxy-6 beta,7 beta; 15 beta,16 beta-dimethylene-3-oxo-1, 4-androstadiene-17 alpha-yl) propionic acid gamma-lactone (spirorenone), a new aldosterone antagonist, and four of its derivatives were studied in comparison with spironolactone in rats. Spirorenone was 8.6 times as potent as spironolactone, but showed a lower affinity for the MCR than the standard. The C1/C2 saturated derivative (compound I) had 7.6 times the antialdosterone potency and 2 times the binding activity of spironolactone. The 17-spiroether derivative of spirorenone (compound II) showed a lower aldosterone antagonistic activity (1.7 the potency of spironolactone) as well as a lower affinity for the MCR (0.5 the affinity of spironolactone). The analogue with a 17 beta-hydroxyl group and a 17 alpha-hydroxypropyl side chain (compound III) possessed a very low binding capacity for MCR (1/10 of that of spironolactone) but still a 1.3 times higher antialdosterone activity than spironolactone. This result is probably due to a transformation of compound III to an active metabolite in vivo. Finally, the derivative with a reversed configuration of the 17-spirolactone ring (compound IV) had no biological activity in vivo and no affinity for the MCR. These results show that spirorenone or one of its active derivatives might lead to a new series of potent aldosterone antagonists.

Adrenalectomy↗
PubMed1984

[Hypotensive properties of nisoldipine. Comparative study in essential, renal and renovascular hypertension].

Calcium antagonists are increasingly used in the treatment of primary and secondary hypertension. A new substance of this group, isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate (nisoldipine, Bay k 5552) inhibits the calcium-induced contraction of arteries and veins in concentrations 5-20 times lower compared to those of nifedipine in vitro. The effect of nisoldipine (10 mg orally) on blood pressure and heart rate in supine and upright position, on serum electrolytes (Na+, K+, Ca2+) and on serum aldosterone and serum hydrocortisone (cortisol) was comparatively studied in patients with essential hypertension (n = 6, 57 +/- 7 years), in patients with hypertension and chronic renal failure (n = 6, 46 +/- 4 years, serum creatinine 2.1 +/- 0.5 mg/100 ml) and in 6 patients with unilateral renal artery stenosis. In patients with essential hypertension, systolic blood pressure (BP) dropped by 26 mmHg; diastolic BP was lowered by 17 mmHg after 150 min compared to placebo. In patients with chronic renal failure, decrement in BP was 25/16 mmHg (systolic and diastolic BP, respectively). In patients with renal artery stenosis, blood pressure declined by 31/18 mmHg after nisoldipine. Serum electrolytes (Na+, K+ and Ca2+) and serum aldosterone as well as serum hydrocortisone remained unchanged. The hypotensive action of nisoldipine seems to be independent of the type of hypertension. However, the hypotensive activity correlates with the level of the baseline blood pressure.

Adult↗
PubMed1983

Structure-activity relationship of new steroidal aldosterone antagonists. Comparison of the affinity for mineralocorticoid receptors in vitro and the antialdosterone activity in vivo.

The ability of 18 steroids with structures similar to spironolactone, progesterone or aldosterone to compete with [3H]aldosterone for binding at rat renal cytosol receptors in vitro and the antialdosterone activity in vivo were tested in comparison with spironolactone. The affinity of these compounds for mineralocorticoid receptors was then compared with their pharmacological action in rats. Replacement of the 17-spirolactone ring by a 17 alpha-hydroxypropyl group and a 17 beta-hydroxyl group resulted in a loss of affinity for the [3H]aldosterone binding sites but not in a reduction in antialdosterone activity in vivo. Compared to spironolactone, C6/C7 unsaturated compounds showed a reduced activity both in vitro and in vivo. Substitution of the 7 alpha-thioacetyl group of spironolactone by a 6,7-methylene group in the beta position (prorenone) increased the affinity to the receptor as well as the biological activity by 52 and 41%, respectively. Introduction of a methyl-group at the D-ring of spironolactone resulted in similar significant drops in activity both in vitro and in vivo. The progesterone like steroids were weak competitors for aldosterone in vitro and in vivo. Two of three aldosterone like steroids (18-deoxyaldosterones) still exhibit mineralocorticoid activity and one analogue could be classified as a weak aldosterone antagonist. The studies show in general that the comparison of the affinity for mineralocorticoid receptor sites with the antimineralocorticoid activity in vivo is a valuable procedure in the search for new antimineralocorticoid substances.

Aldosterone↗
PubMed1982

[Primary hyperaldosteronism: differentiation between aldosterone-producing adenoma and idiopathic adrenocortical hyperplasia (author's transl)].

The regulation of aldosterone secretion by sodium restricted and enriched diet was assessed in 21 patients with primary aldosteronism for differentiation between unilateral aldosterone-producing adenoma and adrenocortical hyperplasia causing autonomous aldosterone hypersecretion. Compared to 10 patients with idiopathic adrenocortical hyperplasia, urinary aldosterone excretion after 4 days of sodium restricted diet was significantly higher in 11 patients with established adenoma (41.3 +/- 16.3 micrograms/24 h vs 19.8 +/- 8.5 micrograms/24 h; P less than 0.005). After six days of sodium loading these differences became even more obvious (35.3 +/- 14.0 micrograms/24 h vs 12.7 +/- 3.7 micrograms/24 h; P less than 0.0005). Sodium excretion did not influence aldosterone secretion in the adenoma group. In patients with hyperplasia both parameters showed a negative correlation (r = -0.522; P less than 0.001). Differentiation without overlap between both patient groups was achieved by comparison of the quotient of aldosterone excretion and serum potassium level during sodium enriched diet.

Adenoma↗
PubMed1982

Antihypertensive effects of captopril and saralasin in essential and renal hypertension.

The antihypertensive effect of captopril and its mechanism of action were studied in patients with essential and renal hypertension. In mild essential hypertension (n = 12), during monotherapy with captopril (50 to 450 mg, 4 to 12 weeks) blood pressure was normalized in seven, improved in two and remained unchanged in three patients, plasma levels of active and acid-activatable inactive renin significantly increased and angiotensin II decreased, whereas no consistent changes in urinary kallikrein excretion occurred. In severe renal (n = 14) and essential (n = 9) hypertension, blood pressure was normalized in eight (seven with renal hypertension), improved in seven and unchanged in eight patients, when captopril (50 to 450 mg, 3 to 15 months) was added to the antihypertensive medication. In one patient with stenosis in a transplanted renal artery reversible renal failure occurred during captopril therapy possibly because of a steep initial decrease in blood pressure, although a toxic effect of the drug cannot be excluded. In another series of 12 renal and 8 essential hypertensive patients, a significant correlation between the acute effect of captopril (within 90 minutes) an saralasin on blood pressure was demonstrated (r=0.71, p less than 0.001). The change in blood pressure after either drug was significantly related to the initial plasma renin concentration. In conclusion, captopril seems to be an effective antihypertensive agent in essential and renal hypertension. Renal function should be monitored during captopril therapy. Our studies suggest that captopril decreases blood pressure by inhibiting the vasopressor action of the renin-angiotensin system.

Angiotensin II↗
PubMed1982

Characterization of a group of essential hypertensives with impaired regulation of aldosterone.

The pattern of aldosterone excretion during high sodium intake in 100 patients with essential hypertension allowed the differentiation of two groups: in the majority of patients (group A, n = 64) aldosterone excretion was suppressed below 6 micrograms/day similar to the normotensive control group. In a second group (group B, n = 36), aldosterone remained above the control range despite forced sodium loading. In group B, serum potassium was significantly lower than in patients of group A (3.81 +/- 0.44 meq/l vs. 4.26 +/- 0.57 meq/l, p less than 0.001). The blood pressure lowering effect of spironolactone (200 mg/d) was more pronounced among patients in group B. Plasma renin values tended to be lower in group B compared to patients with suppressed aldosterone. Infusion of Angiotensin II (0.1 - 2 micrograms/kg/min) led to a similar relative rise of plasma aldosterone levels in both groups despite higher baseline values in group B. The exact mechanism of the impaired regulation of aldosterone in a subgroup of patients with essential hypertension remains to be elucidated.

Adenoma↗