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Biomedical subjects

G Bönner

Publications and source records attributed to G Bönner.

At least 55 records · Page 3Linked to original sources
PubMed1989

Role of kinins and prostacyclin in blood pressure regulation.

The main vasodepressor hormone systems are the kallikrein-kinin systems and the vascular prostacyclin. Kallikreins release kinins which are the biological active compounds of the kallikrein-kinin systems. Kinins are one of the most potent vasodilators reducing systemic blood pressure by diminution of vascular resistance. The reduction in blood pressure is strongly dose related. Prostacyclin develops similar effects on blood pressure as kinins. There is a close relationship between kinins and prostacyclin since kinins stimulate prostacyclin synthesis very effectively. In arterial hypertension there is a lack in kallikrein-kinin and prostacyclin activity. This could also be shown under experimental conditions in spontaneously hypertensive and in Dahl salt-sensitive rats. In clinical studies these experimental results were confirmed in primary hypertension. The blood pressure response to exogenous vasodepressor hormones is increased in hypertensives suffering from reduced endogenous vasodilator activity. In the knowledge of reduced vasodilator activities in primary hypertension the stimulation of kinins by prostacyclin will be of major interest in the management of primary hypertension. In the last years some drugs have been investigated with regard to their kinin prostacyclin stimulating effect, but only angiotensin converting enzyme inhibitors, linolenic acid and cicletanin seemed to induce therapeutic prostacyclin stimulation. However, it remains unclear whether these drugs develop their blood pressure lowering effect by stimulation of the discussed vasodilators or by some other effect.

Animals↗
PubMed1989

Detection of renal impairment in cases of chronic abuse of analgesics by administration of desamino-D-arginine vasopressin.

An early diagnosis of renal dysfunction is particularly important in patients with chronic abuse of analgesics. First morphological changes in cases of analgesic nephropathy are found in the renal medulla. Therefore, urinary osmolarity as well as the urinary excretion of cyclic adenosine monophosphate (AMP) and kallikrein were measured after application of desamino-D-arginine vasopressin (DDAVP) as parameters of the renal tubular function in 21 patients with normal creatinine clearance and a regular, excessive use of analgesics. The results were compared with those of 17 healthy volunteers and 8 patients with chronic renal insufficiency after analgesic nephropathy. In patients with analgesic nephropathy the urine osmolarity after 12 h of thirst was 367 +/- 28 mOsm/kg and did not increase after DDAVP. The results obtained from healthy volunteers were 781 +/- 39 mOsm/kg. Half of the patients with chronic misuse of analgesics had lower values of urine osmolarity after thirst and DDAVP compared to the reference area of healthy subjects. Similar results were found when the effect of DDAVP under conditions of water-loading was tested. The excretion of cyclic AMP as a second messenger of DDAVP and of kallikrein did not differ between patients with chronic abuse of analgesics and healthy volunteers. The excretion of kallikrein in patients with manifest analgesic nephropathy, however, was decreased. Thus the renal concentration test with DDAVP proved to be useful in early diagnosis of renal dysfunction caused by analgesics.

Adult↗
PubMed1988

[Angiotensin-converting enzyme and 1,25-dihydroxyvitamin D3 in hypercalcemia of unknown origin].

Sarcoidosis of the kidneys and liver without radiologically demonstrable lung involvement in a 44-year-old woman was shown to be the cause of a hypercalcaemia syndrome. The hypercalcaemia was presumably due to an increased production of 1,25-(OH)2-vitamin D3 which--like the increased angiotensin converting enzyme--is produced in the epithelioid and giant cells. Corticoid treatment normalized serum calcium and ACE levels and improved renal function. These observations demonstrate that measurement of ACE and 1,25-(OH)2-vitamin D3 levels is helpful in the differential diagnosis of hypercalcaemia, in view of the possibility of sarcoidosis, and should be among the diagnostic tests.

Adult↗
PubMed1988

Relationship between plasma atrial natriuretic peptide and left atrial and left ventricular involvement in essential hypertension.

In order to investigate the role of cardiac hypertrophy in atrial natriuretic peptide (ANP) secretion in patients with essential hypertension, plasma levels of ANP were measured after overnight rest in 36 patients with untreated hypertension and in 31 normotensive controls. In the hypertensive subjects, plasma levels were correlated with left ventricular (LV) and left atrial abnormalities detected by chest X-ray, electrocardiogram (ECG) and M-mode echocardiography. Plasma ANP levels in patients with hypertension averaged 146 +/- 27 pg/ml compared to 46 +/- 7 pg/ml in the normotensive subjects (P less than 0.001). In patients with hypertension a significant correlation was found between ANP and supine systolic blood pressure (r = 0.54, P less than 0.001) and between ANP and diastolic blood pressure (r = 0.38, P less than 0.05). Furthermore, plasma ANP levels were correlated with total heart volume (r = 0.68, P less than 0.01), LV mass (r = 0.525, P less than 0.001), LV posterior wall thickness (r = 0.39, P less than 0.05), Sokolow-Lyon index (r = 0.721, P less than 0.001) and end-diastolic diameter of the left atrium (r = 0.334, P less than 0.05). The results suggest a contribution of LV and left atrial abnormalities to ANP secretion in essential hypertension.

Adult↗
PubMed1988

[Effect of atrial natriuretic peptide (ANP) on the renal kallikrein-kinin system in normotensive and spontaneously hypertensive rats].

Injection of atrial natriuretic peptide (ANP) induces marked diuresis, natriuresis and less marked blood pressure reduction. These effects are similar to those of renal kallikrein-kinin system (rKKS). In this study we investigated the influence of ANP on rKKS of rats. ANP was injected intravenously in male normotensive (WKy) and spontaneously hypertensive rats (SHRsp) as a bolus of 3.5 micrograms atriopeptin III. ANP induced, in both groups of rats, a marked increase in diuresis and natriuresis, while blood pressure decreased significantly. Renal plasma flow and urinary excretion of potassium increased only a little. The observed changes were similar in both strains of rats and there was no statistically significant difference except the lower potassium stimulation in the SHRsp than in the WKy (p less than 0.05). In regard to the basal activity of the rKKS there was a significant difference between the two strains of rats. The activity of renal kallikrein in urine and of kininase II in plasma was reduced in the SHRsp about 50%, while renal kinin excretion in urine was markedly enhanced in these rats, if compared to the WKy controls. In both groups of rats renal kallikrein and kinin excretion was stimulated by ANP for a short time and, simultaneously, total kininogen in plasma decreased after the injection of ANP. The increment of renal kallikrein excretion in urine was much less marked in the SHRsp than in the WKy rats. The reduced kallikrein stimulation was compensated by the reduced kinin degradation by kininase II in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Do kinins have significance for the antihypertensive effect of angiotensin-converting enzyme inhibitors?].

Inhibition of angiotensin I converting enzyme (ACE, kininase II) results in a reduced release of angiotensin II and in an accumulation of kinins. By pretreatment with inhibitors of the kallikrein-kinin systems, the blood pressure lowering effect of the ACE-inhibitors will be diminished. These results suggest that potentiation of kinins will participate in the blood pressure reduction by ACE-inhibitors. However, other studies contradict this hypothesis, showing that the inhibition of kallikrein-kinin systems per se will often result in a reduction of stimulated renin activity. Even the measurement of kinins in the blood cannot clarify the role of kinins in ACE-inhibition. Some new investigations discuss only a local and tissue-specific enhancement of kinins after ACE-inhibition, but up to now strong evidence for participation of kinins by local mechanisms in the action of ACE-inhibitors is still missing.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Plasma levels of atrial natriuretic peptide are raised in essential hypertension during low and high sodium intake.

Plasma levels of alpha-human atrial natriuretic peptide (hANP) were measured in 17 patients with primary hypertension (11 females, 6 males, aged 22-61; blood pressure systolic 154 +/- 7 mmHg, diastolic 92 +/- 4 mmHg) and in 9 normotensive controls (4 males, 5 females, aged 20-71; blood pressure systolic 117 +/- 4 mmHg, diastolic 76 +/- 2 mmHg) during unrestricted sodium diet, at the 4th day of a low sodium intake (40-60 mEq/day) and at the 6th day of sodium loading (280-320 mEq/day) both after an overnight rest and after 4 h of upright posture. In the controls, plasma levels of hANP at 8:00 a.m. were lowered from 73 +/- 11 to 49 +/- 7 pg/ml during low sodium diet and increased to 128 +/- 37 pg/ml after high salt intake. Plasma ANP levels were significantly lower after 4 h of upright posture during unrestricted, low and high sodium intake. In the hypertensive group, plasma ANP levels were elevated during unrestricted diet (203 +/- 43 pg/ml), during the low sodium period (139 +/- 31 pg/ml), and after high sodium intake (267 +/- 63 pg/ml) compared to the controls. All levels were lowered by upright posture. The absolute decrease was more pronounced compared to the normotensives, the relative decline was similar in both groups. In the hypertensives, plasma ANP levels significantly correlate with systolic and diastolic blood pressure (r = 0.468, r = 0.448, P less than 0.05) and with urinary aldosterone during unrestricted diet (r = 0.536, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Diminution by captopril of the diuretic, natriuretic and kallikrein stimulating action of furosemide by reduction in its renal secretion.

The effect of furosemide (40 mg iv) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated without and with pretreatment by captopril (100 mg po). Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly (UNaV pre-C: +15, 1 +/- 2.1 ml/min vs. post-C: 7.0 +/- 0.3 ml/min; p less than 0.001). Similar changes in urinary kallikrein and kinin excretion were observed after captopril pretreatment, but because of the great coefficient of variation these changes did not reach statistical significance. The reason for the reduced activity of furosemide after captopril pretreatment was the diminished proximal-tubular secretion of furosemide, as it could be shown by direct measurement of the drug in urine. After furosemide injection changes in plasma aldosterone concentration paralleled changes in renal kallikrein and kinin excretion. However, after captopril there was a sharp dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion.

Adult↗
PubMed1987

The analytical value for kinin concentration in blood depends on the antiserum used in the bradykinin radioimmunoassay.

Recently published blood kinin concentrations are subject a wide scatter, due to sampling time and technique. In our study we tested the influence of the used antibradykinin antiserum on the measured kinin concentration in blood. Blood was collected from the anticubital vein by a teflon cannula and inactivated immediately by hydrochloric acid in the syringe. Subsequent extraction was performed using diethylether, n-butanol, distilled water and Biorex-70. The blood extract containing the kinins was divided into four samples and measured by four radioimmunoassays using different antibradykinin antibodies. All four assays were performed under standard conditions and at the same time. The resulting kinin values were similar in two assays: 7.4 +/- 2.6 ng/l and 5.6 +/- 1.3 ng/l. In the two other assays, however, the measured kinin concentrations differed markedly from these values: 127.5 +/- 46.7 ng/l and 693.0 +/- 85.7 ng/l. These results indicate clearly that the antibody used in the assay can be a major factor determining the range of the recorded kinin concentration.

Bradykinin↗
PubMed1987

In vivo effects of camostat mesilate on plasma kallikrein, plasma kininase II and renal kallikrein of man.

N,N-Dimethylcarbamoylmethyl-4-(4-guanidino-benzoyloxy)phenylacetat e methanesulfonate (camostat mesilate) is reported to be an effective inhibitor of plasma kallikrein. It was shown in vitro to inhibit not only plasma kallikrein, but also renal kallikrein and plasma kininase II. These inhibitory activities, however, were very weak. The inhibition of plasma kallikrein in human plasma was limited in time, since a rapid reactivation of plasma kallikrein was noticed when samples were incubated at room temperature. In order to establish whether camostat mesilate was able to inhibit plasma kallikrein, kininase II and renal kallikrein also in vivo the inhibitory activity of camostat mesilate on these enzymes was studied in 5 healthy volunteers. After an oral intake of a single dose of 600 mg of camostat mesilate, plasma kallikrein was inhibited significantly, while kininase II in plasma was unaffected. Renal kallikrein activity determined by urinary excretion of active kallikrein remained unchanged after camostat mesilate intake. Thus, the results demonstrate that camostat mesilate in vivo inhibits only plasma kallikrein and has no effect on the activity of kininase II or renal kallikrein.

Adult↗
PubMed1987

Angiotensin I in peritoneal dialysis fluid improved hypotension: a case report.

In a bilateral nephrectomized woman undergoing continuous ambulatory peritoneal dialysis, angiotensin I instilled intraperitoneally with the dialysis fluid prevented the fall in systemic blood pressure at peritoneal dialysis and elevated, in high doses, the systemic blood pressure in a dose-dependent manner over the whole observation period. The blood pressure lowering effect could be completely reversed by infusion of the angiotensin II receptor antagonist, saralasin. However, some side effects observed, like increased motility of gut, diarrhea and abdominal pain probably will limit the application of the drug in clinical routine.

Angiotensin I↗
PubMed1986

Measurement of plasma prokallikrein independent of inhibitors and interfering enzymes.

A new method to determine plasmaprokallikrein independently of its inhibitors is described. By ion exchange chromatography with DEAE-A-50 Sephadex plasmaprokallikrein can be separated from its inhibitors Cl-esterase inhibitor, alpha 2-macroglobulin, alpha 1-antitrypsin (protease inhibitor) and antithrombin III as well as from other enzymes like plasmin, Hagemann factor and glandular kallikrein, which can interfere with the chromogenic substrate of the amidolytic assay (S 2302) used to determine plasmakallikrein activity. Furthermore, this method also allows the measurement of plasmaprokallikrein in heparinized plasma, since heparin was separated by this chromatography technique from plasmaprokallikrein too. The enzymatic activity of activated plasmakallikrein was not changed by the ion exchange chromatography. Normal values of the plasmaprokallikrein content in plasma were in the range of 2.57 +/- 0.12 U/ml of plasma (n:42; X +/- SEM). No influence on plasmaprokallikrein activity of age and sex was found.

Enzyme Activation↗
PubMed1986

Hypotensive effect of bradykinin in normotensives and patients with renovascular hypertension.

Bradykinin is one of the most potent vasodilators and in the kidney it develops a marked diuretic and natriuretic action. The natriuretic effect of the peptide is mediated by prostaglandins. The mechanism of bradykinin induced vasodilation, however, is not yet known. Therefore, in this study the blood pressure lowering effect of bradykinin was investigated in five normotensive volunteers. Bradykinin was injected intravenously in doses between 0.001 and 7.5 micrograms/kg of body weight. Intraarterially measured blood pressure decreased in a dose related manner from 0.25 to 1.0 micrograms/kg. Changes in oral salt intake (10 to 300 nmol Na+/d) had no effect on the action of bradykinin as well as pretreatment with either indomethacin (2 X 50 mg) or propranolol (80 mg). Captopril (25 mg) potentiated the blood pressure lowering effect of bradykinin about 20-fold. In four patients with renal hypertension bradykinin provoked a more marked reduction in arterial blood pressure, while potentiation by captopril was not different in the hypertensives if compared to the normotensives. The results of our studies show that bradykinin lowers blood pressure by a direct mechanism, which acts independently of salt intake, beta-receptors and prostaglandins. Inhibition of inactivation of bradykinin by captopril enhances its activity markedly. In renal hypertension the arterial vessels are more sensitive to bradykinin than in normotension, probably indicating a lack of endogenous kinins in these patients.

Blood Pressure↗
PubMed1986

Sodium loading raises urinary cortisol in man.

It has been suggested that cortisol secretion is modified by sodium intake. We therefore studied the pituitary-adrenal axis by measuring diurnal rhythms of ACTH and cortisol levels in serum of 10 normal control subjects after 4 days of low sodium diet (intake 40 mEq/day) and after 6 days of high sodium diet (intake 320 mEq/day). Urinary excretion of aldosterone-18-glucuronide and free cortisol were determined at the end of each diet. Urinary aldosterone excretion declined from 17.9 +/- 2.6 to 2.8 +/- 1.1 microgram/day and urinary cortisol increased from 26.2 +/- 6.2 to 36.8 +/- 13.8 micrograms/day during low and high sodium intake. In contrast, plasma ACTH and serum cortisol measured every two hours for a 24-h period were similar both during low and high sodium intake. The results suggest an altered handling of cortisol by the kidney during high salt intake.

Adrenocorticotropic Hormone↗
PubMed1986

Inhibition by FOY of kininase II in human plasma.

In this investigation we studied the inhibitory effect of FOY S 983 (gabexate mesilate) and FOY S 980 (camostate mesilate) on the kininase II activity in human plasma in vitro. Both compounds were able to inhibit kinase II, however, compared to captopril or EDTA only very weakly. The inhibitory effect of FOY S 983 or FOY S 980 could be diminished neither by NaOH-induced hydrolysis of the inhibitor nor by dialysis or ultrafiltration, but could be clearly reduced by dialysis against ZnCl2 solution. The inhibition of kininase II activity in human plasma by FOY S 983 was due to its 6-guanidinocaproate component probably acting as Zn2+-complexing agent. The ethyl 4-hydroxybenzoate component of FOY S 983 had no inhibitory effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Blood viscosity: a pathogenetic factor in the development of essential hypertension?

Inhibition of the ouabain-sensitive Na-K-ATPase by digoxin significantly decreases erythrocyte deformability (5). Since first a decrease in this transport system has been discussed as a pathogenetic factor in the development of essential hypertension and second an increase in blood viscosity, due to an increased hematocrit has been observed in elderly hypertensives, hemorheology and sodium transport systems were examined in adolescent hypertensives and compared with age-matched normotensive controls. 73 normotensives (N; mean blood pressure 127/80 mmHg) and 53 hypertensives (H; mean blood pressure 147/94 mmHg) aged 23-27 yrs were randomly selected from an epidemiological survey, covering 1342 adolescents. While apparent whole blood viscosity at different shear rates, hematocrit, plasma fibrinogen were not significantly different, erythrocyte deformability, measured with a positive pressure filter system (pore phi 5 mu) and expressed as Q = delta P/ery.susp.Hct 10%/delta P/plasma was significantly attenuated with Q = 1.77 +/- 0.05 in H, compared to 1.64 +/- 0.04 in N (p less than 0.05) The decrease in erythrocyte deformability was not accompanied by an inhibition of the Na-K-pump nor of total K+-uptake in erythrocytes, both measured with the 86Rb uptake. There was only a slight increase in Na+-excretion in urine of 184.4 + 12.2 mval in H, compared to 162.0 +/- 10.4 mval in N (n.s.). K-/+-excretion and serum electrolytes did not show any difference. Whether the decrease in erythrocyte deformability may contribute to an increase in peripheral vascular resistance in essential hypertension has to be further clarified.

Adult↗
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↗