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Biomedical subjects

W Kreusser

Publications and source records attributed to W Kreusser.

At least 37 records · Page 2Linked to original sources
PubMed1983

Cardiac function in experimental uremia.

In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.

Animals↗
PubMed1982

Vascular effects of parathyroid hormone (PTH).

PTH causes dose dependent transient vasodilatation in various vascular beds, specifically renal, coeliac, coronary, but not osseous. It has an acute dose-dependent hypotensive effect in the intact animal which is not mediated by alpha- or beta-adrenergic, cholinergic or histaminergic mechanisms. Aortic medial smooth muscle cells respond to PTH with an increase of cAMP, cGMP and, presumably via protein kinase, with activation of phosphorylase B kinase. The acute vasodilatory effect of PTH is antagonised by indomethacin and diclofenac as well as by ouabain, suggesting that the membrane Na-K pump and prostaglandins are involved in PTH-induced vasodilatation. Parathyroidectomy and a high calcium diet attenuate the rise of arterial pressure in experimental hypertension, pointing to some permissive effect of PTH for development hypertension. This is most likely due to long term effects of PTH on vessel wall calcium content and exchange. This chronic effect of PTH may explain the high prevalence of hypertension in patients with primary hyperparathyroidism.

Animals↗
PubMed1982

Dysfunction of the adrenergic system in phosphate depleted rats.

Plasma catecholamines and vascular response to noradrenaline were studied in phosphate depleted rats. Phosphate depletion was induced in rats by dietary phosphorus deprivation for 6 weeks. Basal plasma concentrations of noradrenaline, adrenaline and dopamine were elevated in phosphate depleted rats compared to pairfed control rats. After exposure to cold (4 degrees C, 45 min) the rise in plasma catecholamines was much more pronounced in phosphate depleted rats. In the isolated perfused rat heart, the uptake of tritiated noradrenaline was unchanged. In the isolated perfused hindlimb preparation the vascular response to noradrenaline, but not to potassium chloride and arginine-vasopressin was significantly diminished in phosphate depleted rats. It is concluded that in phosphate depletion sympathetic activity is elevated and vascular response to noradrenaline diminished.

Animals↗
PubMed1982

Diminished response of ovarian cAMP to luteinizing hormone in experimental uremia.

In prepuberal female rats with acute bilateral nephrectomy or chronic subtotal nephrectomy, the increase of ovarian cAMP concentration in response to submaximal doses of luteinizing hormone (LH 10 micrograms) and human chorionic gonadotropine (hCG 2.5 IU) was diminished (CO + 2.5 IU hCG 488 +/- 49 pmoles cAMP/mg protein; NX + 2.5 IU hCG 366 +/- 56. P less than 0.05). The cAMP response to follicle stimulating hormone (FSH) was unchanged. The abnormality was found both after administration of LH in vivo and incubation of ovaries with LH in vitro. Similarly, plasma estradiol concentrations in response to submaximal hCG stimulation were diminished. Basal cAMP concentrations and cAMP concentrations after maximal stimulation were unchanged. The defect was observed both in ovaries of untreated prepuberal rats, of pregnant mare serum (PMS)-treated rats (follicular phase) and PMS/hCG-treated rats (luteal phase). Diminished ovarian cAMP response to LH was observed both in parathyroid intact and in parathyroidectomized rats. Administration of 1,25(OH)2D3 in physiological doses (60 ng/kg) to acutely uremic rats restored diminished ovarian cAMP response to submaximal LH stimulation irrespective of parathyroid status. The effect of 1,25(OH)2D3 could not be reproduced by hypercalcemia resulting from intraperitoneal calcium injection. In vivo administration of indomethacin further diminished ovarian cAMP response in uremic animals and had no effect in control animals. Incubation of ovaries with PGE1 and PGE2 increased basal and stimulated cAMP concentrations and abolished the difference between control and uremic animals. The diminished response of ovarian cAMP content to submaximal doses of hCG was not corrected by bromocriptine (1 mg/kg) despite normalization of hyperprolactinemia. The present study shows diminished ovarian cAMP and plasma estradiol response to LH in experimental uremia. It documents a role of 1,25(OH)2D3 and prostaglandins in the genesis of this abnormality.

Alprostadil↗
PubMed1982

Haemodynamics and myocardial metabolism of phosphorus depleted dogs: effects of catecholamines and angiotensin II.

The responses of arterial pressure and myocardial contractile force (VPM) to infusion of angiotensin II, noradrenaline and orciprenaline were examined in twelve dogs during a control phase, after 30 days of dietary phosphorus deprivation and after 21 days of phosphorus repletion. In the phosphorus depletion period, animals had low skeletal and heart muscle Pi content, low magnesium, ATP and creatine phosphate in skeletal and heart muscle with no change of ADP, AMP or energy charge. In the basal state, VPM was diminished with no change of end-diastolic and systolic pressure. Infusion of angiotensin II caused a significantly smaller rise of arterial pressure (angiotensin II resistance), and the stimulatory effect of noradrenaline and orciprenaline on VPM was diminished (catecholamine resistance). These effects were reversible with Pi repletion. In phosphorus depletion, arterial concentrations were increased for lactate, unchanged for FFA and decreased for acetoacetate/beta-hydroxybutyrate. Unchanged myocardial extraction of lactate or beta-hydroxybutyrate and preserved cell Pi uptake for glycogenolysis were observed. The initial rate of uptake of calcium and concentrating ability of myocardial sarcoplasmic reticulum were unchanged.

Angiotensin II↗
PubMed1982

Effect of parathyroid hormone, calcitonin and growth hormone on cAMP content of growth cartilage in experimental uraemia.

The response of proximal tibial growth cartilage cAMP content to different hormonal stimuli, i.e. parathyroid hormone, calcitonin and somatotropic hormone was evaluated in rats with bilateral or subtotal nephrectomy. In uraemic rats, basal cAMP content of growth cartilage was unchanged. Administration of 1-34 PTH in vivo or incubation of growth cartilage with 1-34 PTH in vitro caused a significantly smaller increment of cAMP in uraemic rats (40 IU PTH in vivo: 11.4 +/- 1.01 pmol cAMP/mg protein; controls 24.0 +/- 2.55; P less than 0.001). This finding implies PTH resistance. Diminished cAMP response in uraemic animals was not changed by pretreatment with 1,25(OH)2D3 or parathyroidectomy. The increment of cAMP content of growth cartilage of uraemic animals was significantly (P less than 0.01) greater after in vivo administration of 10 IU calcitonin (46.1 +/- 4.89 pmol/mg protein; control: 29.0 +/- 3.99) or incubation of cartilage with calcitonin in vitro. This finding implies overresponsiveness to calcitonin. Neither in acute nor in chronic uraemia, STH caused a significant change of cartilage cAMP or cGMP content, but STH stimulated 3H-thymidine incorporation into chondrocytes of rats with 5 days uraemia (solvent 2.98 +/- 0.51 x 10(3) cpm per cartilage; STH 5.08 +/- 0.34; P less than 0.05) and caused significant improvement of longitudinal growth of rats with 20 days uraemia.

Animals↗
PubMed1980

Lack of involvement of sarcoplasmic reticulum in myopathy of acute phosphorous depletion.

Acute and chronic hypophosphatemia are known to cause metabolic myopathy. It has been proposed that impaired Ca transport in subcellular membranes is involved in its genesis. In the present study, calcium transport in the sarcoplasmic reticulum (SR), concentrations of ions or nucleotides and transmembrane potential were investigated in muscles of acutely hypophosphatemic rats, i.e. animals with chronic dietary phosphorous deprivation (PD) and superimposed acute hypophosphatemia resulting from the administration of insulin and glucose. Despite hypophosphatemia and low muscle phosphorous concentration, no significant change of the initial rate of Ca uptake or Ca concentrating ability was observed in the SR of PD rats. Storing capacity was decreased; this may result from altered vesicle geometry. Water content, Na concentration, the concentration of several nucleotides and transmembrane potential of muscle were unchanged in PD rats. The findings document that no intrinsic abnormality of vectorial Ca transport is present in the SR of acutely hypophosphatemic PD animals.

Animals↗
PubMed1980

[Phosphate-depletion (author's transl)].

The essential and critical role of inorganic phosphate has been known in veterinary medicine and experimental research on animals for decades. However, only recently has the phosphate depletion syndrome found widespread attention by clinicians. Hypophosphatemia is usually observed in the following clinical situations:chronic alcoholism, recovery phase of diabetic ketoacidosis, administration of phosphate-free solutions in parenteral nutrition, severe respiratory alkalosis, and infusion of fructose. Disturbed organ function in hypophosphatemia is the result of a depletion of inorganic phosphate in the cytoplasm of somatic cells. Such phosphate depletion may be due to either of the following mechanisms or a combination of both. (1) Negative external phosphate balance resulting from phosphate loss in urine or feces or (2) translocation of phosphate from the extracellular into the intracellular space with or without concomitant negative external phosphate balance. In principle, phosphate depletion interferes with the function of all somatic cells. In acute phosphate depletion, the clinically most important disturbances are observed in striated muscle (rhabdomyolysis with myoglobinuric acute renal failure), heart muscle (acute heart failure), and hematological systems (hemolysis, disturbed leukocyte and thrombocyte functions). In contrast, in chronic phosphate depletion skeletal abnormalities (osteomalacia) predominate. Organ disturbances are thought to result from diminished synthesis of ATP and other organic phosphate esters and/or from hypoxia secondary to changes in erythrocyte 2,3-DPG.

Acute Kidney Injury↗
PubMed1980

Function of the sarcoplasmic reticulum (SR) in hypophosphatemic myopathy.

Lipid composition and Ca2+ transport properties were examined in the isolated sarcoplasmic reticulum of non-exercised muscles of markedly phosphorus depleted rats. Phosphorous depletion with a fall of plasma Pi from 8.04 +/- 0.85 to 2.56 +/- 0.48 mg/dl was accompanied by a decrease in muscle Pi and ATP content and by a significant decrease in the phospholipid/protein ratio of sarcoplasmic reticulum. The phosphatidyl -choline/phosphatidyl-ethanolamine ration in sarcoplasmic membranes was increased. Storing capacity for Ca2+ was significantly diminished. In contrast, there was no significant change of kinetic parameters of Ca2+ transport, i.e. of the initial rate of uptake and concentrating ability. These findings do not necessarily exclude changes of cytosolic Ca2+ concentration in phosphate depletion, but they exclude alterations of intrinsic kinetic properties of the sarcoplasmic reticulum as a cause of any such potential changes.

Animals↗
PubMed1980

Abnormalities of glycogen metabolism in cardiomyopathy of phosphorous depletion.

In severely phosphorous depleted rats, no change of glycogen content or activities of enzymes catalysing glycogen synthesis or breakdown was observed. In contrast in heart muscle, a decrease of myocardial glycogen content was observed which was accompanied by increased activity of phosphorylase and decreased activity of synthetase. It is assumed that these changes result from increased catecholamine action secondary to an activation of the sympathetic nerve system resulting from impaired contractile state of the myocardium. The changes observed are analogous to those found in heart failure.

Animals↗
PubMed1979

[Vitamin D metabolism in kidney insufficiency: disorders of an endocrine regulatory zone].

The vitamin metabolite 25(OH)D is transformed into the active secosterole 1.25(OH)2D3 in the proximal tubular epithelium of the kidney. This transformation is disturbed in patients with renal insufficiency. However, this review shows that presumably not all vitamin D dependent disturbances in patients with renal insufficiency are explicable merely as the consequence of reduced renal synthesis of 1.25(OH)2D3 secondary to nephronal loss. In incipient renal failure, vitamin D dependent functions (calcemic action of PTH, intestinal absorption of Ca) are disturbed. Yet, circulating 1.25(OH)2D3 levels are slightly elevated. This finding is compatible with an inadequate response of the renal 1-alpha-hydroxylase system to activating stimuli (hyperparathyroidism, hypocalcemia, fasting hypophosphatemia) and/or end-organ resistance to the action of 1.25(OH)2D3. Osteomalacia in renal insufficiency cannot entirely be explained as the consequence of a reduction of the serum-concentration of any of the known vitamin D metabolites [25(OH)D3; 1.25(OH)2D3; 24.25(OH)2D3]. The relatively poor response of osteomalacia of uremic patients to the administration of 1.25(OH)2D3 leads to the question of whether other vitamin D metabolites or non-vitamin D related factors are important in its genesis. Critical information is lacking with respect to 1.25(OH)2D3 receptors, post receptor events and interaction between vitamin D metabolites and PTH in bone cells of such patients. A specific action of 1.25(OH)2D3 on longitudinal growth of uremic children has been described. However, several clinical and experimental studies failed to provide evidence of normalization of growth by 1.25(OH)2D3 and failed to show differences in this respect between vitamin D and 1.25(OH)2D3. Currently, it remains undecided whether vitamin D metabolites affect PTH secretion, and if so which vitamin D metabolite is involved. Clarification of this problem is of paramount importance for the therapeutic suppression of the parathyroids of uremic patients. Vitamin D metabolites play an important role in some organ functions unrelated to homeostasis of Ca-Pi-metabolism (e.g. muscle, testis, pancreas, etc). The loss of such function is of potential importance in the genesis of the uremic syndrome and its imcomplete reversal by hemodialysis.

Absorption↗