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A Kribben

Publications and source records attributed to A Kribben.

72 records · Page 4Linked to original sources
PubMed1987

Sympathetic nervous activity and noradrenaline reactivity during angiotensin converting enzyme inhibition.

The effect of the angiotensin converting enzyme inhibitor ramipril on catecholamine disposition and noradrenaline reactivity was studied in normotensive volunteers. In the first study 5 mg of ramipril or placebo was given 3 times at 12-hour intervals in a randomized, double-blind, cross-over manner (n = 10). In the second study, ramipril 10 mg daily was given for 2 weeks (n = 6). Noradrenaline reactivity increased significantly (p less than 0.05) both in short- and long-term application, while blood pressure decreased (p less than 0.01). Sulfoconjugated plasma noradrenaline decreased significantly (p less than 0.05) possibly indicating a decrease in sympathetic tone. These findings suggest that a decrease in sympathetic tone could contribute to the blood pressure-lowering effect of ramipril, whereas the increase in noradrenaline reactivity is probably a consequence of the primary change in sympathetic activity.

Adult↗
PubMed1987

Effects of acute hypermagnesaemia on intracellular calcium concentration and adrenergic activity.

The effects of acute hypermagnesaemia on intracellular free calcium and adrenergic activity were investigated in six normotensive volunteers given intravenous magnesium sulphate for 3 h. The free calcium concentration in platelets decreased after the first hour of infusion (P less than 0.05), but did not remain significantly depressed after 2 and 3 h of continued infusion. Plasma noradrenaline increased during the infusion (P less than 0.05), with no change in plasma adrenaline. The results demonstrate that the effects of intravenous magnesium sulphate on free intracellular calcium and plasma catecholamines are similar to those described with calcium antagonists.

Adult↗
PubMed1987

Effects of nitrendipine and tiapamil on 45Ca2+ influx and on platelet aggregation.

The effects of the dihydropyridine derivative nitrendipine and of the phenylalkylamine derivative tiapamil on 45Ca2+ influx was determined in platelets in vitro and on platelet aggregation ex vivo. Thrombin-stimulated 45Ca2+ influx was inhibited by 10 mumol/l nitrendipine and 100 mumol/l tiapamil. ADP- and adrenaline-induced platelet aggregation were inhibited in normotensive volunteers following short-term administration of nitrendipine (20 mg b.i.d.) but not after tiapamil (225 mg t.i.d.). Therefore, mechanisms other than the inhibition of Ca2+ influx should be considered to be responsible for inhibition of platelet aggregation by nitrendipine ex vivo.

Adult↗
PubMed1987

Regulation of alpha 2-adrenoceptor density in normotensive and hypertensive man.

We examined normotensive and hypertensive subjects in order to determine whether changes in platelet alpha 2-adrenoceptor density following alterations in plasma noradrenaline are related to changes in noradrenaline (NA) reactivity. Noradrenaline reactivity, plasma NA, alpha 2-adrenoceptor density, and adenylate cyclase activity were measured before and after a 24-h infusion of NA at a subpressor dose (0.02 micrograms/kg per min, n = 13), and also after application of drugs known to increase (nifedipine and furosemide) or decrease (clonidine) plasma NA. Measurements were obtained 60 min after nifedipine (20 mg in a single dose, n = 13), after 3 weeks on furosemide (30 mg twice a day, n = 8) and after 1 week on clonidine (150 micrograms three times a day, n = 5). Infusion of NA decreased alpha 2-adrenoceptor density (P less than 0.01) and NA reactivity (P less than 0.05). Nifedipine decreased alpha 2-adrenoceptor density and NA reactivity (P less than 0.01 for both) in patients with essential hypertension. The alterations in alpha 2-adrenoceptor densities were paralleled by a decreased adrenaline-induced inhibition of adenylate cyclase activity (P less than 0.01). Furosemide decreased alpha 2-adrenoceptor density (P less than 0.01), the fraction of high-affinity binding sites (P less than 0.01) and NA reactivity (P less than 0.05) in normotensive subjects. Following clonidine all three parameters, alpha 2-adrenoceptor density, the fraction of high affinity sites and NA reactivity, increased (P less than 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1987

Platelet intracellular free calcium and hypertension.

Platelet intracellular free calcium concentration was assessed by the quin-2 method in 38 patients with essential hypertension and in 35 normotensive subjects. The concentrations were found to be significantly higher in the hypertensive patients (p less than 0.05); however, there was a wide overlap between the values of both groups. In addition, we determined platelet intracellular free calcium in another model of increased blood pressure, the blood pressure elevation following administration of the synthetic mineralocorticoid fludrocortisone. Administration of 0.8 mg fludrocortisone per day to eight normotensive volunteers resulted in a pronounced increase in intracellular free calcium after the first week and a decrease toward control levels thereafter, while blood pressure remained elevated throughout the period of fludrocortisone administration. Our findings suggest that an increase in intracellular free calcium concentration is a transitory phenomenon and not directly related to the blood pressure elevation.

Adult↗
PubMed1985

Free intracellular calcium in essential hypertension. Effects of nifedipine and captopril.

The acute effects of nifedipine (20 mg sublingually) and of captopril (12.5 mg orally) on blood pressure and on platelet intracellular free calcium were investigated in 11 and 12 patients, respectively, with essential hypertension. Platelet calcium was measured by the Quin 2 method. Application of both drugs resulted in a significant fall in blood pressure within 60 min. Platelet calcium, however, was lowered by nifedipine only. There was no correlation between blood pressure reduction and changes in platelet calcium. Platelet intracellular free calcium concentration was 99 +/- 3 nmol in 30 normotensive subjects and 109 +/- 5 nmol (+/- s.e.m.) in 26 patients with essential hypertension (P < 0.05). There was a wide overlap between the values of normotensives and hypertensives. Thus there is no positive evidence of an increased platelet intracellular free calcium concentration in a large proportion of patients with essential hypertension.

Adult↗
PubMed1985

Sympathetic tone and pressor response to noradrenaline during mineralocorticoid-induced blood pressure rise in man.

To gain insight into the role of the sympathetic nervous system in the development of mineralocorticoid hypertension, we determined noradrenaline and adrenaline in plasma and urine before, during and after administration of the synthetic steroid, fludrocortisone, for a period of 6 weeks in normotensive volunteer subjects. In addition, pressor reactivity to exogenous noradrenaline, platelet alpha 2- and lymphocyte beta 2-receptors, and platelet intracellular free calcium were determined. Fludrocortisone induced a fall in free and sulpho-conjugated plasma noradrenaline and after 6 weeks, a rise in free and sulpho-conjugated noradrenaline excretion. The number of alpha 2- and beta 2-adrenergic binding sites decreased. A marked increase in platelet free intracellular calcium was found after the first week of fludrocortisone administration followed by a decrease in the following weeks. Reactivity to exogenous noradrenaline was found to be enhanced and this could be a factor contributing to the development of hypertension. Whereas the decrease in plasma noradrenaline observed would suggest a diminution in sympathetic tone, the finding of a rise in urinary noradrenaline excretion after 6 weeks of steroid administration in the presence of suppressed plasma levels points to an increased renal sympathetic drive. The decreased number of platelet alpha 2- and lymphocyte beta 2-receptors observed would also be consistent with the assumption of an increased sympathetic tone.

Adult↗
PubMed1984

Effect of nifedipine and verapamil on alpha-receptor-activation in patients with essential hypertension.

The question of whether the hypotensive effect of calcium entry blockers involves an interaction with alpha-adrenergic receptors was examined. The effect of nifedipine subl. (20 mg, n = 9) and of verapamil p.o. (160 mg, n = 9) on the pressor effect of the unselective alpha-adrenergic agonist noradrenaline, as well as on 3H-yohimbine binding to platelet alpha 2-adrenoceptors was studied in patients with essential hypertension. In addition, the effect of nifedipine on reactivity to the selective alpha 1-adrenergic agonist phenylephrine was investigated (n = 9). Nifedipine caused a significant reduction of reactivity to noradrenaline (P less than 0.01), along with a significant decrease in binding sites (P less than 0.01). Affinity to the alpha 2-receptors was unchanged. Verapamil, although equally effective in lowering blood pressure, had no effect on the pressor response or binding sites. The pressor effect of the alpha 1-agonist phenylephrine was reduced (P less than 0.01) by nifedipine. Nifedipine may therefore affect both alpha 1- and alpha 2-adrenoceptors in patients with essential hypertension. Since verapamil did not affect the pressor response to noradrenaline or yohimbine-binding, the interaction with alpha 2-adrenoceptors does not appear to be a general prerequisite for the hypotensive action of calcium entry blockers.

Adult↗
PubMed1983

Characterization of Mg-ATP-dependent Ca2+ transport in cat pancreatic microsomes.

Mg-ATP-dependent 45Ca2+ uptake and Ca2+-ATPase activity have been examined in isolated microsomes obtained by differential centrifugation and in purified subcellular fractions obtained by Ficoll-sucrose density centrifugation in the presence of mitochondrial inhibitors. Mg-ATP-dependent 45Ca2+ uptake increased with increasing EGTA-buffered free [Ca2+], reaching a maximum of 2 nmol 45Ca2+ X 15 min-1 X mg prot-1 at 2 mumol/1 [Ca2+] in the incubation medium. Half-maximal 45Ca2+ uptake was at approximately 0.2 mumol/1 [Ca2+]. Maximal Ca2+ -Mg2+ -ATPase activity was 130 nmol X 15 min-1 X mg prot-1 at 2 mumol/l [Ca2+], with an apparent Km of approximately 0.3 mumol/l [Ca2+]. The Ca2+ ionophore A23187 (10(-6) mol/l), the mercurial compounds mersalyl (10(-5) mol/l) and CH3ClHg (10(-3) mol/l), as well as La3+ (10(-4) mol/l), vanadate (10(-4) mol/l), and saponin (50 micrograms/mg prot), abolished Mg-ATP-promoted 45Ca2+ uptake. In the absence of Mg2+, ATP did not provoke 45Ca2+ uptake. Using the purified smooth membrane fraction (F1) from the Ficoll-sucrose density gradient (enrichment of Na+-K+-ATPase specific activity by ninefold and of NADH-cytochrome c reductase by threefold as compared with total tissue homogenate), Mg-ATP-dependent 45Ca2+ uptake correlated better with Na+-K+-ATPase (r = 0.97) than with the smooth endoplasmic marker NADH-cytochrome c reductase (r = 0.52). No correlation was found with RNA, the marker for rough endoplasmic reticulum. We conclude that pancreatic plasma membranes contain a Ca2+-Mg2+-ATPase that represents the Ca2+ extrusion system from acinar cells. It is also possible that vesicular membrane structures associated with the plasma membrane, or endocytotic plasma membrane vesicles, take up Ca2+ and represent an intracellular Ca2+ pool.

Adenosine Triphosphate↗
PubMed1982

Calcium uptake into acini from rat pancreas: evidence for intracellular ATP-dependent calcium sequestration.

Intracellular ATP-dependent Ca2+-sequestration mechanisms were studied in isolated dispersed rat pancreatic acini following treatment with saponin or digitonin to disrupt their plasma membranes. In the presence of 45Ca2+ concentrations less than 10(-6) mol/liter, addition of 5 mmol/liter ATP caused a rapid increase in 45Ca2+ uptake exceeding the control by fivefold. ADP mimicked the ATP effect by 50 to 60%, whereas other nucleotides such as AMP-PNP, AMP-PCP, CTP, UTP, ITP, GTP, cAMP and cGMP did not. Maximal ATP-promoted Ca2+ uptake was obtained at 10(-5) mol/liter Ca2+. Inhibition of Ca2+ uptake by mitochondrial inhibitors was dependent on the Ca2+ concentration, indicating the presence of different Ca2+ storage systems. Whereas the apparent half-saturation constant found for mitochondrial Ca2+ uptake was approximately 4.5 X 10(-7) mol/liter, in the presence of antimycin and oligomycin (nonmitochondrial uptake) it was approximately 1.4 X 10(-8) mol/liter. In the absence of Mg2+ both ATP- and ADP-promoted Ca2+ uptake was nearly abolished. The Ca2+ ionophore and mersalyl blocked Ca2+ uptake, Electron microscopy showed electron-dense precipitates in the rough endoplasmic reticulum of saponin-treated cells in the presence of Ca2+, oxalate and ATP, which were absent in intact cells and in saponin-cells without ATP or pretreated with A23187. The data suggest the presence of mitochondrial and nonmitochondrial ATP-dependent C2+ storage systems in pancreatic acini. The latter is likely to be located in the rough endoplasmic reticulum.

Adenosine Diphosphate↗
PubMed1981

Analysis of Ca2+ fluxes and Ca2+ pools in pancreatic acini.

45Ca2+ movements have been analysed in dispersed acini prepared from rat pancreas in a quasi-steady state for 45Ca2+. Carbamyl choline (carbachol; Cch) caused a quick 45Ca2+ release that was followed by a slower 45Ca2+ 'reuptake'. Subsequent addition of atropine resulted in a further transient increase in cellular 45Ca2+. The data suggest the presence of a Cch-sensitive 'trigger' pool, which could be refilled by the antagonist, and one or more intracellular 'storage' pools. Intracellular Ca2+ sequestration was studied in isolated acini pretreated with saponin to disrupt their plasma membranes. In the presence of 45Ca2+ (1 microM), addition of ATP at 5 mM caused a rapid increase in 45Ca2+ uptake exceeding the control by fivefold. Maximal ATP-promoted Ca2+ uptake was obtained at 10 microM Ca2+ (half-maximal at 0.32 microM Ca2+). In the presence of mitochondrial inhibitors it was 0.1 microM (half-maximal at 0.014 microM). 45Ca2+ release could still be induced by Cch but the subsequent reuptake was missing. The latter was restored by ATP and atropine caused further 45Ca2+ uptake. Electron microscopy showed electron-dense precipitates in the rough endoplasmic reticulum of saponin-treated cells in the presence of Ca2+, oxalate and ATP which were absent in intact cells or cells pretreated with A23187. The data suggest the presence of a plasma membrane-bound Cch-sensitive 'trigger' Ca2+ pool and ATP-dependent Ca2+ storage systems in mitochondria and rough endoplasmic reticulum of pancreatic acini. It is assumed that Ca2+ is taken up into these pools after secretagogue-induced Ca2+ release.U

Adenosine Triphosphate↗
PubMedDate not supplied

Cystatin C: efficacy as screening test for reduced glomerular filtration rate.

Serum cystatin C, a cysteine proteinase inhibitor, has been proposed as a marker of glomerular filtration rate (GFR). Serum cystatin C, serum creatinine and creatinine clearance were measured in 226 patients with various nephropathies, covering the entire range of renal function, to evaluate the efficacy of cystatin C as a screening test to detect reduced creatinine clearance in comparison to creatinine. Subgroups of 53 patients with glomerular and 26 patients with tubular impairment were compared to assess whether cystatin C performed differently in either glomerular or tubular impairment. Cystatin C detected reduced creatinine clearance with higher sensitivity (97 vs. 83%), and higher negative predictive value (96 vs. 87%) compared to creatinine. In parallel, 95% sensitivity of cystatin C as derived from receiver-operating characteristic plot was significantly higher (p < 0.05). In the subgroups with glomerular or tubular impairment, cystatin C and creatinine did not significantly differ with regard to efficacy. Serum cystatin C is as efficacious as serum creatinine to detect reduced GFR as measured by creatinine clearance. The efficacy of cystatin C as a screening test may even be superior compared to creatinine. In addition, the efficacy of cystatin C is independent of either glomerular or tubular impairment.

Adolescent↗
PubMedDate not supplied

Pathophysiology of acute renal failure.

Acute renal failure (ARF) is a common renal disease affecting up to 5% of all hospitalized patients, with a higher prevalence of 10-30% in patients in critical care units (1-3). Despite advances in the management of critically ill patients and technological advances in renal replacement therapy, the high mortality of patients with ARF has not changed over the last decades and remains above 50% (4-6). Moreover, as a consequence of more advanced medical therapy and more complicated surgical interventions in older and multimorbid patients, the number of patients with ARF is increasing (1, 4, 5). Moreover, ARF itself increases the risk to develop additional complications that can be deleterious. Recently, an independent association between ARF and mortality has been shown in patients following administration of radiocontrast media in an intensive care unit and in patients following cardiac surgery (6, 7). Following radiocontrast media the mortality of patients with ARF was increased five fold and following cardiac surgery sixteen-fold as compared to patients with the same underlying disease without ARF. The pathophysiology of ischemic ARF is reviewed with the emphasis on the following mechanisms: Increased fractional excretion of sodium, Activation of tubuloglomerular feedback, Cytoskeletal disruption, Tubular obstruction, Vascular mechanisms. The following mediators will also be discussed: Calcium, Cysteine proteases, Nitric oxide, Adhesion receptors and integrins.

Acute Kidney Injury↗