[Effect of upper arm circumference on RR measurement].
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Adult↗
Biomedical subjects
M Tepel
Publications and source records attributed to M Tepel.
[Clinical approach in polycystic kidney disease with recurrent hematuria].
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Carcinoma, Renal Cell↗
Diadenosine polyphosphates regulate cytosolic calcium in human fibroblast cells by interaction with P2x purinoceptors coupled to phospholipase C.
The effects of diadenosine pentaphosphate (AP5A), and diadenosine hexaphosphate (AP6A) on the cytosolic-free Ca2+ concentration ([Ca2+]i) were evaluated in cultured human fibroblast cells (HF cells) using the fluorescent dye technique. AP5A, and AP6A concentration-dependently increased [Ca2+]i in HF cells. The addition of 10 mumol/1 AP5A and AP6A significantly increased [Ca2+]i in HF cells from 71 +/- 3 nmol/1 (n = 184) to 241 +/- 39 nmol/1 (n = 11; P < 0.001 compared to resting value) and to 227 +/- 26 nmol/1 (n = 23; P < 0.001), respectively. The purinoceptor P2 blockers, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), inhibited the diadenosine polyphophate-induced [Ca2+]i increase, whereas the P2y purinoceptor blocker, reactive blue, had no effect. Adenosinetriphosphate (ATP) and the P2x agonist, alpha 1 beta-methylene-ATP also significantly increased [Ca2+]i in HF cells, whereas the P2y agonist methylthio-ATP showed only a small [Ca2+]i response. Diadenosine polyphosphates mainly induced transplasmamembrane Ca2+ influx as was confirmed by experiments in the absence of extracellular Ca2+ or by manganese quenching studies. Organic (verapamil) and inorganic Ca2+ channel blockers (NiCI2) significantly reduced the AP6A induced transplasmamembrane Ca2+ influx. The inhibitor of phosphatidylcholine-specific phospholipase C, D609, significantly reduced the effect of diadenosine polyphosphates on [Ca2+]i in HF cells. It is concluded that diadenosine polyphosphates regulate transplasmamembrane Ca2+ influx after occupation of P2x receptors via activation of phosphatidylcholine-specific phospholipase C and hence of voltage-operated Ca2+ channels.
Bridged-Ring Compounds↗
Increased lymphocytic Na+/H+ exchange activity after hemodialysis: evidence for an endogenous inhibitor of Na+/H+ exchange in patients with end-stage renal failure.
The Na+/H+ exchange antiport activity was measured in lymphocytes from 16 patients with end-stage renal failure pre- and postdialysis. In addition the effect of the patients' plasma on lymphocytes from healthy subjects was tested. Resting pH (pHi) was not significantly different in lymphocytes pre- and postdialysis. On the other hand, the Na+/H+ exchange activity was significantly lower in lymphocytes before hemodialysis (6.22 +/- 0.73 x 10(-3) pHi/s) than after hemodialysis (9.32 +/- 1.58 x 10(-3) pHi/s; n = 16; p < 0.05). The buffer capacity was not significantly different before and after hemodialysis. The incubation of lymphocytes from healthy control subjects with plasma from patients with end-stage chronic renal failure significantly reduced the lymphocytic Na+/H+ exchange activity. The addition of ultrafiltrate also significantly reduced the Na+/H+ exchange activity in lymphocytes from healthy control subjects. The study indicates the existence of an endogenous inhibitor of the Na+/H+ exchange that is accumulated in plasma from patients with end-stage chronic renal failure.
Adult↗
Low concentrations of ouabain increase cytosolic free calcium concentration in rat vascular smooth muscle cells.
1. Low ouabain concentrations in the nanomolar range significantly increased cytosolic free calcium concentration. 2. The ouabain-induced cytosolic free calcium concentration increase was due to transplasmamembrane calcium influx, which could be prevented in the absence of extracellular calcium or by addition of the calcium channel blocker nifedipine. 3. The amount of stored cellular Ca2+, as determined by the thapsigargin-induced cytosolic free calcium concentration increase, was also enhanced by 1 nmol/l ouabain. 4. It is concluded that low ouabain concentrations affect intracellular cytosolic free calcium concentration homoeostasis.
Animals↗
Diadenosine polyphosphates induce transplasma membrane calcium influx in cultured glomerular mesangial cells.
The effects of diadenosine tetraphosphate (AP4A) diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) on the cytosolic-free calcium concentration ([Ca2+]i) were evaluated in cultured rat glomerular mesangial cells (MCs) using the fluorescent dye technique. The addition of 10 mumol L-1 AP4A, AP5A or AP6A significantly increased [Ca2+]i in MCs by 57 +/- 9 nmol L-1 n = 17; P < 0.01), 76 +/- 27 nmol L-1 (n = 9; P < 0.01) or 65 +/- 12 nmol L-1 (n = 18; P < 0.01) respectively. In the absence of extracellular calcium, there was no significant change in [Ca2+]i in MCs after administration of diadenosine polyphosphates, indicating that these agents induce transplasma membrane Ca2+ influx. AP6A significantly enhanced the angiotensin II-induced changes in [Ca2+]i in MCs. The AP5A-induced transplasma membrane Ca2+ influx was inhibited by the P2 purinoceptor blockers suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), but was not affected by the adenosine A1 receptor blocker 8-cyclopentyl-1.3-dipro-pylzanthine (CPDPX). Adenosine triphosphate (ATP) and adenosine 5'-O-(3-thio)triphosphate (ATP-gamma S) increased [Ca2+]i in MCs, whereas alpha, beta-methylene ATP had no effect on [Ca2+]i in MCs. Measurements of diacylglycerol and phosphatidic acid showed that AP5A and AP6A also stimulated phospholipase C, but had no effect on phospholipase D. The inhibition of phosphatidylcholine-specific phospholipase C significantly reduced the AP5A-induced [Ca2+]i increase. In summary, diadenosine polyphosphates induce Ca2+ influx through P2 purinoceptors and may be involved in the local regulation of vascular resistance evoked by the Ca(2+)-dependent contractile response of mesangial cells.
Adenosine Triphosphate↗
Vascular actions of diadenosine phosphates.
1. Diadenosine phosphates were isolated from platelets, adrenal gland and autonomic nerves. The presence of diadenosine phosphates in storage pools releasable into the circulation suggests an important role in the control of blood pressure, and potentially to a modulation of the actions of catecholamines. 2. Besides a role of the diadenosine phosphates in platelet aggregation, these agents have potent vasoactive properties. Vasoactive actions of the diadenosine phosphates were demonstrated in numerous vascular models including most of the physiologically important elements of blood pressure regulation. Mostly, the vasoactive action depends on the number of phosphates in the diadenosine phosphates. Vasodilation can be observed in intact vessels after administration of Ap2A, Ap3A and Ap4A whereas contraction is affected by Ap5A and Ap5A and Ap6A. Vasocontraction induced by the diadenosine phosphates in vascular smooth muscle cells is mediated by an increase in intracellular free Ca2+. 3. In vivo, intravenous injection of Ap4A lowers blood pressure whereas injections of Ap5A and Ap6A caused a prolonged increase in blood pressure. In blood, in contrast to ATP, diadenosine phosphates are relatively long-lived molecules, suggesting that the action of the latter is of intermediate time span. In a similar manner to the vasoconstrictor angiotensin II, diadenosine phosphates also act as mitogens. It can be assumed that diadenosine phosphates may be involved in pathophysiological events of circulation including hypertension and atherosclerosis.
Animals↗
Na+/H+ exchange in patients with mild chronic renal failure.
Cytosolic pH (pHi) and Na+/H+ exchange activity were measured in lymphocytes from 22 patients with mild chronic renal failure, and 21 age- and sex-matched normotensive healthy control subjects using the fluorescent dye technique. The basal pHi in resting lymphocytes was not significantly different in both groups tested (control, pHi 7.18 +/- 0.04; patients with mild chronic renal failure, 7.17 +/- 0.05). The initial rate of pHi recovery immediately after intracellular acidification with 100 mmol/l propionic acid, representing the maximum Na+/H+ exchange activity, was significantly higher in lymphocytes from patients with mild chronic renal failure (7.10 +/- 0.52 dpHi/s, mean +/- SEM) when compared with control subjects (5.42 +/- 0.47 dpHi/s; p < 0.05). No significant correlation between Na+/H+ exchange activity and blood pressure could be obtained in patients with mild chronic renal failure. Furthermore, there was no relationship of Na+/H+ exchange activity to cytosolic pH or extracellular pH. It is concluded that an enhanced Na+/H+ exchange activity can be detected in patients with mild chronic renal failure and may not be related to the significant abnormalities of electrolyte and acid-base metabolism commonly observed in patients with end-stage renal failure or on hemodialysis.
Acid-Base Equilibrium↗
Pulse pressure correlates in humans with a proscillaridin A immunoreactive compound.
Endogenous digitalis-like factors in humans are presumably cardenolides and bufadienolides. To test whether bufadienolide-like substances may circulate in human blood, we used antibodies from rabbits against the bufadienolide proscillaridin A to measure the concentration of cross-reacting material in human plasma with an indirect enzyme-linked immunosorbent assay. IgG had an apparent affinity of 2 x 10(-9) mol/L for proscillaridin A. It was specific for bufadienolides and did not cross-react with cardenolides or several steroid hormones. Extraction of human plasma with ethanol and fractionation of this extract over a high-performance liquid chromatographic reverse-phase C18 column with a propanol/isopropanol gradient resulted in the separation of three peaks of increasing hydrophobicity (ED1, ED2, ED3) that inhibited the sodium pump of human red blood cells and cross-reacted with proscillaridin A antibodies. The concentration of the proscillaridin A immunoreactivity ED1 in normotensive subjects had a geometric mean of 0.1 nmol/L, with a dispersion factor of 8.77. ED1 correlated positively in a group of 60 normotensive subjects, 22 patients with hypertension, and 19 patients with chronic renal failure with mean arterial blood pressure (log ED1 [nmol/L] = 0.013 x mm Hg-2.17, r = .25, P < .05), systolic pressure (log ED1 [nmol/L] = 0.010 x mm Hg-2.23, r = .32, P < .01), and pulse pressure (log ED1 [nmol/L] = 0.019 x mm Hg-1.80, r = .38, P < .0001). There was no correlation with other parameters of the donors. We conclude that several substances cross-reacting with proscillaridin A antibodies and inhibiting the sodium pump of human red blood cells circulate in human blood. The level of one of these substances (ED1) correlates with mean arterial and pulse pressures.
Adult↗
High density lipoproteins enhance the Na+/H+ antiport in human platelets.
In the present study, we investigated the effect of high density lipoproteins 3 (HDL3) on Na+/H+ exchanger activity and cytosolic pH (pHi) in human platelets. HDL3 alone failed to affect pHi, but preincubation with HDL3 significantly enhanced the Na+/H+ antiport activation brought about by acidification with 100 mM sodium propionate or stimulation with 0.05 U/ml thrombin. the stimulatory effect of HDL3 was unaffected by indomethacin excluding a role for cyclooxygenase products. The HDL3 effect was not mediated by Ca2+/calmodulin-dependent protein kinase as HDL3 failed to increase cytosolic free calcium concentration. However, the potentiating effect of HDL3 was completely blocked in the presence of the protein kinase C inhibitor, bisindoylmaleimide and the phosphatidylcholine-specific phospholipase C inhibitor, D609. Furthermore, the effect of HDL3 was abolished after covalent modification of HDL3 with dimethylsuberimidate and was not observed in platelets from Glanzmann thrombasthenia type 1 which do not express GP IIb/IIIa, as well as in platelets preincubated with anti-GP IIb/IIIa polyclonal antibodies. We conclude that HDL3 enhances the sodium propionate- and thrombin-induced Na+/H+ antiport activity in human platelets via binding to GP IIb/IIIa and activation of protein kinase C and phosphatidylcholine-specific phospholipase C.
Blood Platelets↗
Depletion of intracellular calcium stores triggers transplasmamembrane chloride influx in human lymphocytes: regulation by tyrosine kinase.
The capacitative regulation of intracellular chloride concentration ([Cl-]i) was measured in intact human lymphocytes using the Cl(-)-sensitive fluorescence dye 6-methoxy-1-(3-sulfonato-propyl)-quinolinium (SPQ). The fluorescence was measured at 433 nm with the excitation wavelength of 344 nm. The emptying of intracellular Ca2+ stores after the specific inhibition of the endoplasmic Ca2+ ATPase by thapsigargin produced a concentration-dependent transplasmamembrane Cl- influx. The thapsigargin-induced Cl- increase was also seen in the absence of extracellular Ca2+, but it was significantly reduced after the addition of the Cl- exchange blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The thapsigargin-induced Cl- increase was significantly reduced after the specific inhibition of tyrosine kinase by genistein or tyrphostin A25. It is concluded that the depletion of intracellular Ca2+ pools triggers transplasmamembrane Cl- influx by a tyrosine kinase-dependent mechanism.
Biological Transport↗
Effect of extracellular Mg2+ concentration on agonist-induced cytosolic free Ca2+ transients.
The modulating effects of extracellular Mg2+ concentration ([Mg2+]o) on vascular contraction are well known. In the present study it was tested how the changes in cytosolic free Ca2+ concentration ([Ca2+]i) induced by various agonists are modified by changes in [Mg2+]o. Extracellular Mg2+ deprivation increased the [Ca2+]i response to arginine vasopressin, to angiotensin II and to thapsigargin, but not to 5-hydroxytryptamine and noradrenaline. Withdrawal of extracellular Ca2+ revealed that extracellular Mg2+ deprivation increased Ca2+ influx, but not Ca2+ release from cellular stores. The findings demonstrate that different responses of [Ca2+]i to agonists may underlie the modulating effect of [Mg2+]o on vascular contraction.
Angiotensin II↗
Dexamethasone-induced sodium influx in human lymphocytes.
We evaluated the direct effects of glucocorticoids on intracellular sodium content and cellular transport systems. Cytosolic free sodium concentration ([Na+]i) was measured in intact human lymphocytes using the sodium-sensitive fluorescent dye sodium-binding benzofuran-isophthalate. Administration of dexamethasone for 60 min increased lymphocytic [Na+]i from 17.6 +/- 2.0 mmol/L to 24.3 +/- 3.9 nmol/L (n = 12; P < 0.01). The dexamethasone-induced [Na+]i increase was abolished in the absence of extracellular sodium, by mifepristone and by actinomycin D. The dexamethasone-induced [Na+]i increase was also seen after inhibition of Na+,K(+)-ATPase by 1 mmol/L ouabain. The present results indicate that dexamethasone produces a trans-plasma membrane sodium influx probably by early occurring genomic effects.
Biological Transport↗
Prognostic value of serum erythropoietin levels in late acute rejection of renal transplants.
Since renal allograft rejection is frequently associated with a blunted erythropoiesis, we investigated erythropoietin (EPO) serum concentrations in 17 patients with acute rejection, eight patients with chronic rejection, and 18 transplant recipients with stable graft function. All rejection episodes were proven by biopsy. Erythropoietin serum levels were significantly reduced in patients with chronic rejection (6.2 +/- 3.4 mU/mL; P < 0.01) compared with individuals with acute rejection (35.6 +/- 33.9 mU/mL) or stable graft function (24.0 +/- 19.7 mU/mL). Suppressed EPO levels were associated with marked anemia in chronic rejection patients. In a subgroup of patients with acute rejection and bad responses to an intensified immunosuppressive regimen or with transplant failure, we found significantly suppressed EPO levels (11.6 +/- 6.1 mU/mL) compared with a subgroup of patients with a beneficial acute rejection outcome (57.0 +/- 34.2 mU/mL; P < 0.01). A correlation between histologic parameters of acute rejection and hormone levels showed that signs of moderate glomerulitis were associated with elevated EPO levels, whereas lesions of moderate tubulitis were associated with low values. We conclude that serum EPO may have prognostic value for rejection outcome in renal transplant recipients.
Acute Disease↗
Transforming growth factor beta 1 modulates angiotensin II-induced calcium influx in vascular smooth muscle.
The modulatory effects of transforming growth factor beta 1 (TGF beta 1) on the angiotensin II (Ang II)-induced increase in cytosolic free calcium concentration ([Ca2+]i) were investigated in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). [Ca2+]i in VSMC was measured using the fluorescent dye fura-2. When TGF beta 1 was applied 30s prior to Ang II, the Ang II-induced [Ca2+]i increase was significantly enhanced in VSMC from SHR (P < 0.05 compared to control), whereas after the preincubation with TGF beta 1 for 30 min, the Ang II-induced [Ca2+]i increase was significantly reduced in VSMC from both strains. Using the manganese-quenching technique, it was confirmed that short-term exposure to TGF beta 1 enhanced the Ang II-induced trans-plasma-membrane calcium influx in SHR. The inhibition of protein kinase C by calphostin C abolished the stimulatory effect of TGF beta 1 on the Ang II-induced [Ca2+]i increase. It is concluded that TGF beta 1 modulates the Ang II-induced calcium handling in VSMC.
Angiotensin II↗
Coenzyme A glutathione disulfide. A potent vasoconstrictor derived from the adrenal gland.
The adrenal gland is involved in the regulation of vascular tone by secretion of vasoactive agents such as catecholamines, neuropeptide Y, or endogenous ouabain. A further potent vasoconstrictor is isolated from bovine adrenal glands and is identified by chromatography, mass spectrometry, UV spectroscopy, and enzymatic cleavage as coenzyme A glutathione disulfide (CoASSG). CoASSG is found in chromaffin granules of adrenal glands and is released from adrenal medulla slices by carbachol. At a concentration of 10(-12) mol/L CoASSG increases renal vascular resistance. Intra-aortic injection of 5 x 10(-10) mol CoASSG increases blood pressure in the intact animal. Besides its vasopressor properties, this substance potentiates the effects of angiotensin II on vascular tone. It is concluded that CoASSG could play a role in blood pressure regulation not only by direct effects but also by modulation of the action of angiotensin II.
Adrenal Glands↗
Lymphocytic Na(+)-H+ exchange increases after an oral glucose challenge.
The effects of oral glucose challenge on plasma glucose concentration, plasma insulin concentration, arterial blood pressure, cytosolic pH (pHi), cytosolic free Na+ concentration ([Na+]i), and cellular Na(+)-H+ exchange activity were investigated in 16 healthy subjects. The pHi, [Na+]i, and Na(+)-H+ exchange activity were measured in intact lymphocytes by using the fluorescent dye technique. The oral glucose challenge significantly increased plasma glucose, plasma insulin, and the lymphocytic Na(+)-H+ exchange activity, measured as change of pHi per second (control [0 hours], 5.20 +/- 0.53 x 10(-3) dpHi/s; 1 hour after glucose administration, 8.28 +/- 1.07 x 10(-3) dpHi/s; 2 hours after glucose administration, 8.15 +/- 1.18 x 10(-3) dpHi/s; P = .002). The lymphocytic Na(+)-H+ exchange was significantly correlated with plasma glucose concentration (r = .357, P = .041). During steady state euglycemic hyperinsulinemic clamp, the Na(+)-H+ exchange activity was not significantly changed compared with baseline values. The study shows that changes of blood glucose levels can induce an acute increase in Na(+)-H+ exchange activity. Systolic blood pressure and Na(+)-H+ exchange activity were significantly (P < .001) but weakly correlated during an oral glucose challenge.
Adult↗
Regulation of rat mesangial cell growth by diadenosine phosphates.
The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations. The growth stimulatory effect exceeded that of ATP, alpha,beta-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insulin-like growth factor-1. To further elucidate the site of action in the cell cycle, RNA and protein synthesis were assessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cytosolic free Ca2+ concentration. It is concluded that AP5A and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease.
Adenosine↗