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Biomedical subjects

J Giese

Publications and source records attributed to J Giese.

At least 55 records · Page 3Linked to original sources

The renin-angiotensin system and kidney function during initial insulin treatment in diabetic man.

Glomerular filtration rate, renal plasma flow, active renin, renin substrate and angiotensin II concentrations were monitored in nine consecutive patients (3 women, 6 men, mean age 31 years) with newly diagnosed, insulin-dependent diabetes. Measurements were performed before and during the initial eight days of intensive insulin treatment. All patients had ketonuria but none had acidosis. Glomerular filtration rate and renal plasma flow were significantly increased at the time of diagnosis as compared with values from normal subjects. A highly significant decline in glomerular filtration rate from 160 +/- 9 (SEM) to 133 +/- 5 ml/min x 1.73 m2 was seen during the initial eight days of treatment (p less than 0.01). Likewise renal plasma flow declined from 601 +/- 33 to 558 +/- 35 ml/min x 1.73 m2 (p less than 0.05). Plasma concentration of renin was within normal range at day 0, and remained unchanged during the eight day study. Also renin substrate concentration was normal and unchanged during the observation period, whereas angiotensin II concentration was low and unchanged. Our study does not support the suggestion that the renin-angiotensin system contributes to the hyperfiltration characteristically found in newly diagnosed insulin-dependent diabetic patients.

Adult↗

Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man.

Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin II (ANG II) step-up infusion of 0.25 and 1.00 ng kg-1 X min. During the 1.00 ng kg-1 X min infusion ANG II plasma concentrations increased from 11 +/- 2 to 48 +/- 6 pg ml-1; i.e., similar to those obtained during acute hypotensive hypovolaemia in man. Mean arterial pressure increased (P less than 0.05) from a resting value of 89 +/- 3 to 97 +/- 5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P less than 0.05) from 36 +/- 4 to 77 +/- 10 pg ml-1 during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0.25 and 1.00 ng kg-1 X min infusion subcutaneous blood flow decreased (P = 0.06) to 67 +/- 20 and 66 +/- 26%, respectively, of control. It is concluded that: (1) ANG II in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) ANG II does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG II do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma ANG II.

Angiotensin II↗

Central role for sodium in the pathogenesis of blood pressure changes independent of angiotensin, aldosterone and catecholamines in type 1 (insulin-dependent) diabetes mellitus.

We studied 73 Type 1 (insulin-dependent) diabetic patients, 18 to 50 years of age, with a diabetes duration of more than five years. Group 1: normal urinary albumin excretion below 30 mg per 24 h (n = 19); group 2: microalbuminuria, 30-300 mg per 24 h (n = 36); and group 3: diabetic nephropathy, above 300 mg per 24 h (n = 18). Fifteen nondiabetic persons matched for sex and age served as control subjects. The sodium intake evaluated on the basis of 24-h urine sodium excretion was similar in patients and control subjects. Blood pressure in groups 1 and 2 and control subjects was below 160/95 mmHg. The blood pressure was increased in group 3 as compared with the other groups (systolic/diastolic 161 +/- 22/101 +/- 9 mmHg vs 131 +/- 13/84 +/- 10, mean +/- SD, p less than 0.0001). Exchangeable sodium was increased in patients (p less than 0.01) and correlated to the mean blood pressure (n = 70, r = 0.41, p less than 0.01). Extracellular volume was increased in patients (p less than 0.05), whereas plasma volume was normal. Supine serum angiotensin II was suppressed in the patients (p less than 0.001). A negative correlation was found between mean blood pressure and supine serum aldosterone (n = 68, r = -0.24, p less than 0.05), and exchangeable sodium and aldosterone (n = 66, r = -0.36, p less than 0.002) in all patients. The catecholamine levels were also suppressed or normal in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

One year antihypertensive treatment with enalapril once daily: clinical and biochemical effects.

The purpose of the study was to evaluate the antihypertensive effect of enalapril administered once daily (q.d.), and to assess the effectiveness of enalapril in achieving sustained blockade of the renin-angiotensin system. The study population comprised 15 patients with uncomplicated, moderate essential hypertension whose blood pressure (BP) was not adequately controlled on hydrochlorothiazide (HCTZ) monotherapy. Enalapril 10-40 mg q.d. produced a significant fall in supine and erect BP (24 h after enalapril) that persisted during 1 year of combination therapy with HCTZ and enalapril. Blood pressure 6 h after enalapril was significantly lower than BP measured 24 h after enalapril, and occasionally at hypotensive levels. Plasma angiotensin II concentration fell significantly after enalapril with reciprocal increases in the plasma concentrations of renin and angiotensin I. The blockade of the renin-angiotensin system was maintained throughout the study. Bradykinin could not be detected in venous blood at any time during the study. We conclude that combination therapy with HCTZ and enalapril once daily is a rational, simple, and effective treatment in patients with moderate essential hypertension.

Adult↗

Progressive central hypovolaemia in man--resulting in a vasovagal syncope? Haemodynamic and endocrine variables during venous tourniquets of the thighs.

Hypotensive functional haemorrhage induced by venous pooling of blood in the legs has been reported to be characterized by a vasovagal reaction. In the present study these observations were extended by determination of the hormonal profile developed during progressive central hypovolaemia and an emotionally induced vasovagal syncope. In six subjects venous pooling resulted in normotensive central hypovolaemia, in one subject hypotensive central hypovolaemia was induced, and one subject experienced an emotionally induced vasovagal syncope. During normotensive central hypovolaemia heart rate increased from 58 +/- 4 to 76 +/- 4 beats min-1 (P less than 0.05) and cardiac output fell from 6.1 +/- 0.4 to 4.1 +/- 0.2 1 min-1. Pulse pressure and central venous pressure decreased from 64 +/- 4 to 53 +/- 4 mmHg, and from 8 +/- 2 to 3 +/- 2 mmHg, respectively. Adrenaline and noradrenaline increased from 87 +/- 10 to 120 +/- 20 pg/ml and from 196 +/- 33 to 370 +/- 50 pg/ml, respectively. Angiotensin II increased from 13 +/- 4 to 36 +/- 6 pg/ml and aldosterone from 63 +/- 9 to 180 +/- 27 pg/ml. In hypotensive central hypovolaemia the decrease in mean arterial pressure was accompanied by a decrease in heart rate and increments in the plasma concentrations of pancreatic polypeptide, indicating increased vagal activity and beta-endorphin, while plasma noradrenaline was unchanged. In emotionally induced syncope heart rate decreased to cardiac arrest for 13 s, associated with increments in the plasma concentrations of pancreatic polypeptide and beta-endorphin. It is concluded that normotensive functional haemorrhage in man is associated with increased sympathetic activity and that the qualitatively similar observations obtained during an emotionally and a hypovolaemic-induced hypotensive episode indicate that the hypotensive functional haemorrhage is characterized by a vasovagal reaction.

Adult↗

Bradykinin in carcinoid syndrome.

Bradykinin concentrations in peripheral venous blood were measured in seven patients with carcinoid syndrome. The diagnosis was based on typical symptoms and raised urinary excretion of 5-hydroxy-3-indole acetic acid; the carcinoid tumour was verified histologically. Two patients were flushing constantly and the other patients had flushing attacks two to 10 times daily. Several blood samples were taken at weekly intervals from six of seven patients. During 30 sampling procedures the patients were flushing during sampling in 12 instances. Bradykinin was measured by a sensitive solid phase radioimmunoassay technique. Blood bradykinin concentration was normal in all patients. Bradykinin is unlikely to be the vasoactive mediator of flushing.

Aged↗

A highly sensitive and reproducible immunoradiometric assay for total human renin using monoclonal antibodies, iodogen labelling and polystyrene star tubes.

A two-site immunoradiometric assay for total renin concentration in human plasma is described. A new type of polystyrene tubes with a special bottom geometry, so-called Star Tubes were used. The lower limit of detection was 2 microIU per ml and the working range from 2 to 2000 microIU per ml. The variation for duplicate determinations on standards and plasma samples was 2.7% and the day to day variation was 4.8%. No significant interferences or cross reactivities were identified. EDTA-plasma was analyzed after dilution with a phosphate buffer. Plasma samples from different patient categories were analyzed. The results were compared with those obtained by our substrate enrichment method after acid activation of the samples had taken place. A linear correlation (r = 0.990) between the results obtained with the two methods was found.

Antibodies, Monoclonal↗

The renin-angiotensin-aldosterone system in normal 85-year-old people.

Active and total plasma renin concentration, as well as plasma angiotensin II, aldosterone and renin substrate concentrations were measured in venous blood samples from 17 normal 85-year-old people at rest. No discernible sex-related differences were seen. Active plasma renin and plasma aldosterone concentrations were significantly lower in the old people compared to a group of normal 40-year-old people. Plasma angiotensin II concentration showed no decrease with increasing age. Active plasma renin concentration constituted approximately 20% of total plasma renin concentration, with a significant correlation between the two renin moieties. The values for plasma renin substrate concentration are similar to those reported for younger age groups. The lack of standardization of methods severely hampers inter-laboratory comparisons of both active plasma renin and total plasma renin concentrations.

Adult↗

Effect of captopril on kidney function in insulin-dependent diabetic patients with nephropathy.

The influence of angiotensin II on kidney function in diabetic nephropathy was assessed by studying the effect of 12 weeks' monotherapy with captopril (25-50 mg twice a day) in 16 hypertensive insulin dependent diabetic patients with persistent albuminuria. In an initial one week randomised single blind trial of captopril versus placebo, captopril (for nine patients) reduced arterial blood pressure from 148/94 (SD11/6) to 135/88 (8/7) mm Hg (p less than 0.05) and albuminuria from 1549 (range 352-2238) to 1170 (297-2198) micrograms/min (p less than 0.05), while glomerular filtration rate remained stable. No significant changes occurred in seven patients treated with placebo. During the 12 weeks of captopril treatment arterial blood pressure in all patients fell from 147/94 (11/6) to 135/86 (13/7) mm Hg (p less than 0.01), albuminuria fell from 1589 (range 168-2588) to 1075 (35-2647) micrograms/min (p less than 0.01), and glomerular filtration rate fell from 99 (SD19) to 93 (25) ml/min/1.73 m2 (p less than 0.01). The renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased concentrations of angiotensin I and renin. The study showed that glomerular filtration rate is not dependent on angiotensin II, that captopril reduces albuminuria, probably by lowering glomerular hypertension, and that captopril represents a valuable new drug for treating hypertension in diabetics dependent on insulin with nephropathy.

Adult↗

Effects of combined therapy with amiloride and hydrochlorothiazide on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in hypertensive patients.

After a run-in period of 8 weeks on a regimen of hydrochlorothiazide (HCT, median dosage 75 mg/day), patients with essential hypertension were randomly allocated to continued hydrochlorothiazide therapy (Group I) or additional treatment with amiloride (Group II, median dosage 15 mg/day, or 5 mg per 25 mg hydrochlorothiazide) for the following 12 weeks. Thereafter all the patients were changed to treatment with a fixed combination tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide (Moduretic), keeping the thiazide dosage unchanged for an additional 12 weeks. In Group I patients there was no change in plasma potassium, total body potassium content or the renin-angiotensin-aldosterone system during the 12 weeks on HCT. When the treatment was changed to Moduretic, significant increases were found of 10% in plasma potassium and 3% in total body potassium content. No important stimulation of the renin-angiotensin-aldosterone system was found. In Group II patients addition of an average of 15 mg amiloride to the hydrochlorothiazide treatment led to significant increases in plasma potassium and total body potassium content of approximately 15% and 4%, respectively. There was also a significant increase in the plasma concentrations of renin, angiotensin II and aldosterone. Reducing the average dose of amiloride to 7.5 mg/day by use of Moduretic did not lead to decrease in plasma potassium or total body potassium content. Plasma concentrations of renin, angiotensin II, and aldosterone were decreased, but the individual changes varied markedly and no significant overall change was found.

Adult↗

Renal handling of angiotensins I and II in patients with renovascular hypertension.

Plasma renin (PRC) and angiotensin I (pANG I) and II (pANG II) concentrations were determined at renal vein catheterization in 38 hypertensive patients suspected of renal or renovascular aetiology. Veno-arterial differences in pANG I across the affected kidney in patients with lateralization of the renin secretion indicated release of angiotensin I (ANG I) in considerable amounts. Veno-arterial differences in pANG II of around zero indicated that generation and elimination of angiotensin II (ANG II) were equal in that kidney. Across the contralateral kidney the veno-arterial differences in PRC and pANG II were both close to zero, while negative differences in pANG II indicated the removal of ANG II. In patients without lateralization of the renin secretion the veno-arterial differences in pANG I were close to zero or positive, those of pANG II being close to zero or negative. In 14 of the 38 patients, data were obtained either during maintenance treatment with captopril or after a single dose of this converting enzyme inhibitor. Systemic PRC and pANG I values were extremely high and pANG II values low. The pANG I gradient across the affected kidney was further increased compared with pre-captopril levels, whereas the contralateral kidney still eliminated ANG I.

Adolescent↗

Converting enzyme inhibition in mild and moderate essential hypertension. II.

In 24 patients with mild/moderate essential hypertension, we studied the effects of captopril with/without hydrochlorothiazide (Htz) on blood pressure, the renin-angiotensin system, blood bradykinin concentration (BBK), plasma volume, exchangeable sodium and glomerular filtration. Daily captopril doses of 75 and 150 mg were equally effective in reducing the blood pressure. Addition of Htz caused further blood pressure reductions. Nineteen patients attained a diastolic blood pressure less than or equal to 90 mmHg. Angiotensin converting enzyme inhibition with captopril led to a fall in plasma concentrations of angiotensin II (PAII) and renin substrate, and an increase in plasma concentrations of renin and angiotensin I. Patients starting with Htz had a higher PAII and subsequently a larger fall in blood pressure on captopril than untreated patients. BBK remained unchanged, indicating that the hypotensive action of captopril does not involve an accumulation of circulating kinin. Body fluid volumes and renal function were not affected by the various treatment regimens.

Adult↗

Hypotension induced by passive head-up tilt: endocrine and circulatory mechanisms.

Circulatory changes and arterial plasma hormone concentrations were measured in seven healthy young adults during 30 and 60 degrees passive head-up tilt with the subjects supported by a saddle. The 30 degrees tilt induced a decrease in pulse pressure (Pp) from 45 +/- 2 to 35 +/- 4 (mean +/- SE) mmHg concomitant with an increase in heart rate (HR) from 58 +/- 4 to 78 +/- 8 beats/min and a marginal increase in mean arterial pressure (MAP). Norepinephrine increased from 180 +/- 20 to 310 +/- 40 pg/ml, aldosterone increased fivefold, and angiotensin II increased from 8 +/- 2 to 22 +/- 7 pg/ml. The 60 degrees tilt initially produced changes, which were qualitatively similar to the 30 degrees tilt. However, after 19 +/- 3 min sudden decreases were seen in MAP (94 +/- 3 to 50 +/- 8 mmHg), in Pp (38 +/- 5 to 18 +/- 4 mmHg), and in HR (90 +/- 7 to 57 +/- 6 beats/min). Concomitantly, epinephrine doubled while norepinephrine remained unchanged; the vagally controlled hormone pancreatic polypeptide increased from 29 +/- 3 to 51 +/- 8 pmol/l, vasopressin from 4 +/- 1 to 126 +/- 58 pg/ml, and angiotensin II from 23 +/- 9 to 35 +/- 12 pg/ml. The hypotensive bradycardiac episode was immediately reversible on termination of the head-up tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Haemodynamic and humoral effects of lower body negative pressure in normal, sodium-replete man during angiotensin-converting enzyme inhibition with captopril.

The significance of the renin-angiotensin system (RAS) for circulatory homeostasis during gravitational stress (10 min of lower body negative pressure, LBNP, at -40 mmHg) was investigated in eight men on liberal sodium intake. The function of RAS was inhibited by a single oral dose of 100 mg captopril, an angiotensin-converting enzyme inhibitor. Plasma concentrations of renin and angiotensin I were normal before and increased after captopril and during LBNP. Plasma concentration of angiotensin II was normal before captopril, increased during LBNP, and fell to low values after captopril. Systolic blood pressure decreased more during LBNP after captopril than in the control situation. In three cases, the LBNP experiment after captopril had to be interrupted due to marked hypotension. Heart rate and plasma concentration of adrenaline increased above pre-captopril levels. In six subjects, plasma concentration of noradrenaline increased more during LBNP after captopril, less in two subjects, whereas the arginine vasopressin concentration increased more after captopril in all five subjects where measurements were available. The results demonstrate that RAS participates in blood pressure homeostasis also in sodium-replete, normal man. The enhanced increases in heart rate and plasma catecholamines after captopril do not suggest that sympathetic reflex activity during gravitational stress is blunted after captopril, in contrast to the evidence from animal experiments.

Adult↗