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Biomedical subjects

M Wehling

Publications and source records attributed to M Wehling.

At least 163 records · Page 9Linked to original sources
PubMed1987

Effects of aldosterone on intralymphocytic sodium and potassium in patients with primary aldosteronism.

In vitro effects of aldosterone have been described with regard to the intracellular sodium and potassium concentrations of human mononuclear leukocytes. In the present paper the in vitro effect of aldosterone on the intracellular sodium and potassium of human mononuclear leukocytes in 6 patients with primary aldosteronism was investigated. Except for one patient with elevated intracellular electrolytes, sodium and potassium in mononuclear leukocytes of patients with aldosteronism without incubation were within the range for normals. In the patients, no significant change of intracellular sodium or potassium was observed during incubation with or without aldosterone (1.4 nmol/l), whereas in normals, the loss of sodium and potassium during incubation without aldosterone was prevented by 1.4 nmol/l aldosterone. This insensitivity to aldosterone indicates that intracellular electrolytes in mononuclear leukocytes of patients with primary aldosteronism are kept in normal ranges by mechanism which are independent of mineralocorticoids and may represent the cellular correlate to the renal 'escape' phenomenon in aldosteronism.

Adult↗
PubMed1987

Effects of clonidine and dihydralazine on plasma ANF and cyclic GMP levels in humans during volume loading.

Acute volume loading increases plasma atrial natriuretic factor (ANF) levels in man and animals. In the present work we have compared the effects of a 1-week oral application of clonidine (2 x 0.075 mg/day) to dihydralazine (2 x 25 mg/day) in eight healthy volunteers on changes in plasma ANF and plasma and urine cyclic GMP levels after acute volume loading with 2 I physiological saline i.v. Basal plasma ANF levels before infusion were decreased by clonidine to 65% of the untreated controls and remained unaltered with dihydralazine. Volume loading increased plasma ANF levels by about 40% in the control and 30% in the dihydralazine treated group, whereas plasma ANF remained unchanged by volume loading in the clonidine-treated group. Dihydralazine increased basal cyclic GMP levels and urinary cyclic GMP excretion by 30 and 90%, respectively. Basal cyclic GMP levels were identical without treatment and after clonidine treatment. Saline infusion increased cyclic GMP levels by 40% in the control and clonidine-treated groups, and by 25% in the dihydralazine-treated group. Urinary cyclic GMP excretion increased by 2.1-, 1.6-, and 1.2-fold, respectively, in the controls, after clonidine, or after dihydralazine. The results of this study suggest that ANF is involved in the hormonal and hemodynamic effects that are induced by clonidine, but not in those induced by dihydralazine.

Adult↗
PubMed1984

Long-term effect of captopril on kidney function in various forms of hypertension.

To study long-term effects of captopril on renal function in patients with various forms of severe hypertension, serum creatinine values were monitored in 76 patients under captopril therapy over a period of up to 3 years. Three different groups were formed: patients with essential hypertension (n = 37); patients with renovascular hypertension (n = 20); patients with renal parenchymatous hypertension (n = 19). In each of the three groups reduction in blood pressure was accompanied by increases in serum creatinine. However, both changes were more pronounced in patients with renovascular hypertension. In this group only the rise in creatinine was statistically significant and showed a slight progression with duration of captopril treatment. Group specific analysis revealed that the increase was smaller in patients with unilateral (n = 16) renovascular disease than in those with bilateral (n = 4) involvement, but in the former it was still significantly higher than in patients with essential or renal parenchymatous hypertension. Separation of patients according to the underlying disease of renovascular hypertension showed that renal function deteriorated less in patients with arteriosclerotic origin (n = 10) than in those with fibromuscular dysplasia (n = 8). Statistical evaluation of subjects with renovascular and essential hypertension still revealed significant differences in creatinine when the patients with initial plasma renin activity (PRA) below and above 6 ng/ml X 3 h were compared separately. A significant correlation (r = 0.73; P less than 0.05) between blood pressure reduction and creatinine changes was obtained only for patients with renovascular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1984

Angiotensin II binding to human mononuclear cells: receptor or free fluid endocytosis?

It has recently been claimed that there are angiotensin II (ANG II) receptors on human mononuclear cells and on platelets and this has been used for investigating the regulation of the renin-angiotensin system in hypertension. We here show the following. Binding kinetics of 125I-labelled ANG II and [3H]ANG II to mononuclear cells were slow (maximum at 90 min) and the same as for [3H]-inulin. As with [3H]inulin there was no binding at 4 degrees C. Release from the cells was slow and incomplete (about 30% after 15 min, 60% after 60 min). Binding was not saturable over a range from 10(-12) to 10(-6) mol of ANG II/l, about 8% of offered peptide being bound at all concentrations. Various inhibitors of free fluid endocytosis exhibited the same inhibition pattern of ANG II binding to mononuclear cells. Therefore uptake of ANG II into mononuclear cells displayed all the features of free fluid endocytosis. ANG II was degraded by carboxypeptidase A. When this degradation was prevented by D-phenylalanine, no binding occurred. In platelet preparations contaminated by 0.3-5% of mononuclear cells, 125I-labelled ANG II was degraded as well. Free fluid endocytosis of the degradation product strongly depended on the percentage of contaminating mononuclear cells. We conclude that there are no ANG II receptors on human mononuclear cells and that their presence on human platelets is doubtful.

Angiotensin II↗
PubMed1983

[Clonidine transdermal therapeutic system in essential hypertension: effect and tolerance].

The antihypertensive efficacy and side effects of a transdermal therapeutic system containing 2.5 mg clonidine (clonidine-TTS) was investigated in 21 patients with essential hypertension over a period of 10 weeks. The system was designed to release 0.1 mg clonidine/24 h. Mean systolic and diastolic blood pressure fell from 160 +/- 17/106 +/- 7 mm Hg to 139 +/- 16/91 +/- 8 mm Hg after 4 weeks and to 135 +/- 14/89 +/- 8 mm Hg after 10 weeks (p less than 0.001). Sufficient blood pressure control was achieved by one clonidine-TTS weekly in 24% and by 2 clonidine-TTS in 33% of the patients. 43% of all cases required additional oral therapy with 50 mg hydrochlorothiazide/day. However, antihypertensive action was accompanied by a high incidence of local skin reactions. These skin reactions with erythema, itching and red papules occurred in 6 of the 21 patients (29%) after treatment with TTS for at least 4 weeks. Patch testing with the various components of clonidine-TTS in 4 patients identified clonidine-allergy of delayed type in 3 cases. Typical clonidine side effects such as fatigue, dry mouth, constipation and sexual disturbances were moderate. It is concluded that clonidine-TTS has a good and continuous antihypertensive action. However, the high incidence of skin reactions limits its use in the treatment of essential hypertension.

Adult↗
PubMed1983

Obesity, hypertension and intracellular electrolytes.

Intracellular activities of sodium and calcium were determined in red cells of patients with obesity. Compared to normal people mean intracellular sodium and calcium were higher in obese patients. However, increased intracellular sodium and calcium could only be observed in those patients with obesity suffering from hypertension or showing a familial disposition to hypertension. In contrast there was no difference in intracellular sodium and calcium between obese normotensives lacking a familial disposition to hypertension and normal people. Thus, our results suggest, that the observed variations in intracellular sodium and calcium in obesity are due to an enhanced blood pressure or a familial disposition to hypertension and not specific for obesity.

Calcium↗
PubMed1983

Altered calcium and sodium metabolism in red blood cells of hypertensive man: assessment by ion-selective electrodes.

Free intracellular calcium [Ca2+]i, sodium [Na+]i and potassium [K+]i were assessed in freeze-thawed human red blood cells (RBC) by ion-selective electrodes. After metabolic depletion by 30 mM 2-desoxy-glucose, [Ca2+]i increased faster and to significantly higher values in RBC from 16 patients with mild to moderate essential hypertension (mean diastolic blood pressure 111 +/- 10 mmHg) than in the RBC of 24 normotensives. The rate of [Ca2+]i increase was 7.0 +/- 3.6 versus 3.7 +/- 4.0 mumol/h/l cells (P less than 0.01) for the first 24 h and 8.1 +/- 4.8 versus 6.4 +/- 3.5 mumol/h/l cells for the following 24 h. [Na+]i before and after 24 h incubation was significantly higher in hypertensives, whereas basal [Ca2+]i and [K+]i before and after incubation were the same in both groups. After Ca loading by ionophore A 23187, the maximum rate of [Ca2+]i extrusion was not significantly lower in intact RBC from hypertensives than in those from normotensives (59.5 +/- 7.8 versus 87.9 +/- 18.1 mumol/min/l cells). These results indicate disturbances in RBC Ca metabolism similar to those observed earlier for Na and K. If generalized, the defect could lead to raised [Ca2+]i in smooth muscle and sympathetic nerve tissue, thus causing increased vascular tone and probably catecholamine release with subsequent arterial hypertension.

Adenosine Triphosphate↗
PubMed1983

Effect of pindolol and propranolol on plasma renin and aldosterone in patients with renal allograft.

To investigate the effect of propranolol and pindolol on renin and aldosterone secretion, blood samples of 12 nephrectomized kidney transplant recipients were taken after 1 hour in supine position and 30 and 60 minutes after posture change. This procedure was repeated after 4 days under pindolol (3 X 5 mg/day) or propranolol (4 X 40 mg/day). Both pindolol and propranolol suppressed the significant orthostatic rise of plasma renin activity (PRA) seen without medication. Pindolol increased basal PRA markedly, whereas basal PRA under propranolol was the same as without betablockers. Plasma aldosterone (PA) showed significant orthostatic rise under all conditions and thus did not parallel PRA under betablockers. Suppression of PRA response to posture change by betablockers indicates that circulating catecholamines may be involved in orthostatic PRA regulation. The intrinsic sympathetic activity of pindolol results in an increase of basal PRA. In nephrectomized renal transplant recipients, postural PA changes do not seem to be triggered by PRA.

Adult↗
PubMed1983

Clonidine through the skin in the treatment of essential hypertension: is it practical?

The antihypertensive effects and side-effects of a clonidine transdermal therapeutic system (clonidine-TTS) were examined over 10 weeks in 22 patients with essential hypertension. The clonidine-TTS containing a 2.5 mg drug reservoir was designed to release 0.1 mg clonidine/24 h for seven days through a micropore rate-controlling membrane. In the total group mean systolic and diastolic blood pressure decreased from 162 +/- 14/106 +/- 4 mmHg to 137 +/- 17/92 +/- 8 mmHg after four weeks and 136 +/- 13/90 +/- 7 mmHg after 10 weeks (P less than 0.001). Five patients (23%) responded well to one clonidine-TTS (diastolic blood pressure less than or equal to 95 mmHg) and seven patients (32%) needed two clonidine-TTS. Additional oral therapy with 50 mg hydrochlorothiazide/day resulted in reduction of blood pressure to normal in six of the remaining 10 patients. This good pressure response was, however, accompanied by a high incidence of local allergic skin reactions of delayed type (type IV) in seven (32%) of the 22 cases. Patch testing with various components of clonidine-TTS which was performed in four of the seven patients showed in three cases allergic contact dermatitis to clonidine. Our results demonstrate a good and sustained antihypertensive action of clonidine-TTS. However, the extraordinarily high incidence of skin allergy to clonidine limits its use in the treatment of essential hypertension.

Administration, Topical↗
PubMedDate not supplied

Rapid actions of aldosterone: lymphocytes, vascular smooth muscle and endothelial cells.

The genomic theory of steroid action has been the unquestioned dogma for the explanation of steroid effects over the past four decades. Despite early observations on rapid steroid effects being clearly incompatible with this theory, only recently has nongenomic steroid action been recognized more widely and led to a critical reappraisal of unsolved questions about this dogma. Evidence for nongenomic steroid effects come from all fields of steroid research now, and mechanisms of agonist action are studied with regard to membrane receptors and second messengers involved. A prominent example of a receptor/effector-cascade for nongenomic steroid effects has been described for rapid aldosterone effects in various cell types, including lymphocytes, cultured vascular smooth muscle, and endothelial cells involving nonclassical membrane receptors with a high affinity for aldosterone, but not for cortisol, and phosphoinositide turnover. As another important second messenger, [Ca2+]i is consistently increased by aldosterone within 1-2 min. In vascular smooth muscle cells, calcium is released from perinuclear stores, while in endothelial cells a predominant increase of subplasmalemmal calcium is seen. Effects are half maximal at physiological concentrations of free aldosterone (0.1 nmol/L), while cortisol is inactive up to 0.1 micromol/L; the classical mineralocorticoid antagonist canrenone is ineffective in blocking the action of aldosterone. The data show that intracellular signaling for nongenomic aldosterone effects also involves calcium, but pathways of cell activation may vary between different cell types. Future research will have to target the cloning of the first membrane receptor for steroids, and the evaluation of the clinical relevance of these rapid steroid effects.

Aldosterone↗