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W Zidek

Publications and source records attributed to W Zidek.

At least 19 recordsLinked to original sources
PubMed1997

Low-density lipoproteins inhibit the Na+/H+ antiport in human platelets. A novel mechanism enhancing platelet activity in hypercholesterolemia.

BACKGROUND: LDL have been reported to augment platelet activation, and increased platelet reactivity has been observed in familial hypercholesterolemia. However, the underlying mechanisms of this putatively atherogenic effect is unknown. Because intracellular pH (pHi) may play an important role in platelet function, we examined the influence of LDL on pHi and Na+/H+ antiport activity in human platelets and compared it with the effect of [3-methylsulfonyl-4-piperidinobenzoyl] guanidine hydrochloride (HOE 694), a selective Na+/H+ antiport inhibitor. METHODS AND RESULTS: Using a fluorescent dye technique, we demonstrated that incubation of platelets with physiological concentrations of LDL or with HOE 694 decreased pHi. In addition, both LDL and HOE 694 inhibited the Na+/H+ antiport in platelets treated with sodium propionate or thrombin. The inhibitory effect of LDL was observed both in normal and in glycoprotein (GP)IIb/IIIa-as well as in GPIIIb (CD36)-deficient platelets and was not influenced by the covalent modification of apolipoprotein B lysine residues, suggesting that specific LDL binding sites were not involved. Thrombin-induced phosphoinositide breakdown, diacylglycerol formation, and Ca2+ mobilization, as well as platelet aggregation and granule secretion, were potentiated by both LDL and HOE 694. pHi and Na+/H+ antiport activity were significantly reduced in platelets from patients with familial hypercholesterolemia. Both parameters were normalized after normalization of LDL levels by apheresis treatment. CONCLUSIONS: LDL inhibits the Na+/H+ antiport most likely via receptor-independent mechanisms, thereby augmenting platelet reactivity. This novel mechanisms explains increased platelet reactivity in patients with familial hypercholesterolemia and may contribute to the atherogenic potential of LDL.

Adult↗
PubMed1997

Identification of endogenous Des-Arg9-[Hyp3]-bradykinin in human plasma with post-source-decay matrix-assisted laser desorption/ionization mass spectrometry.

In the present study, the purification and sequence analysis of a peptide extracted from human plasma is described. After three chromatographic steps in one of the plasma fractions, a molecular mass of 920 Da was determined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. Further analysis with post-source-decay (PSD)-MALDI-MS revealed an amino acid sequence arg-pro(pro-gly+16)-phe-ser-pro-phe. With the data given from the spectrum, it was impossible to clarify the partial sequence (pro-gly+16). A comparison with a data base suggested that the sequence is very similar to des-arg9bradykinin (arg-pro-pro-gly-phe-ser-pro-phe). But many fragment masses, including the mass of the parent ion of the unknown peptide, are 16 Da larger than the corresponding fragment masses of des-arg9-bradykinin. The interpretation of the fragment pattern does not allow determination of the position of the amino acid that is 16 Da larger. With automated Edman sequence analysis of the fraction of interest, three more major component peptides in this fraction were observed, which were not detected with MALDI-MS. Nevertheless, with the help of the Edman sequence data it was possible to identify the unknown amino acid in the PSD-MALDI-MS sequence as hydroxyproline at the third position. In conclusion, the existence of des-arg9[hyp3]-bradykinin (arg-pro-hyp-gly-phe-ser-pro-phe) in human plasma is described. Furthermore, the study demonstrates that PSD-MALDI-MS and automated Edman sequence analysis complement each other if single unknown peptides from mixtures are to be sequenced.

Bradykinin↗
PubMed1997

High-signal lesions in the midbrain on T1-weighted MRI in an HIV-infected patient.

In addition to opportunistic infections, neoplasms or cerebrovascular complications, metabolic encephalopathies are a classical cause of diffuse brain dysfunction in HIV infection and are frequent in the terminal stage. We report an HIV-infected patient with symmetrical, focally increased signal in the midbrain on proton density-and T1-weighted MRI without corresponding high signal on T2-weighted images or on CT. While the precise nature and cause of this uncommon finding is not fully understood, the available evidence suggests that these lesions might represent a novel metabolic encephalopathy.

AIDS Dementia Complex↗
PubMed1997

Differential effects of diadenosine phosphates on purinoceptors in the rat isolated perfused kidney.

1. The activation of various purinoceptors in rat renal vasculature by P1,P2-diadenosine pyrophosphate (Ap2A), P1,P3-diadenosine triphosphate (Ap3A), P1,P4-diadenosine tetraphosphate (Ap4A), P1,P5-diadenosine pentaphosphate (Ap5A), P1,P6-diadenosine hexaphosphate (Ap6A) was studied by measuring their effects of perfusion pressure of a rat isolated perfused kidney. 2. The vasoconstrictive response to Ap5A was completely due to P2x purinoceptor activation, that to Ap4A and Ap6 was P2x purinoceptor mediated to a large extent, as evidenced by the inhibitory effects of suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS). 3. The vasoconstrictive effects of Ap2A and Ap3A were mostly due to stimulation of A1-receptors, as shown by the inhibitory effect of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 4. The vasoconstrictive response to Ap6A was partially insensitive to A1 and P2x purinoceptor blockers. 5. In raised tone preparations Ap2A and Ap3A evoked vasodilatation, which was blocked by the A2 receptor blocker, 3,7-dimethyl-1-propargylxanthine (DMPX). 6. In raised tone preparations Ap4A evoked vasodilatation when the P2-purinoceptors were blocked by suramin. 7. The activation of different purinoceptor subtypes by diadenosine phosphates critically depends on the number of phosphate groups.

Adenosine↗
PubMed1997

Influence of proteinuria on long-term transplant survival in kidney transplant recipients.

Long-term prognosis in kidney transplant recipients depends on multiple factors. To investigate whether mild proteinuria within the first 6 months following transplantation is a determinant of the long-term function and survival of kidney transplants, 357 patients transplanted between 1980 and 1990 were retrospectively examined over a period of 5 years. 25.5% of the patients developed an early proteinuria between 0.25 and 1.0 g/day over 6 or more months. This group was well matched concerning gender, age of recipient, underlying disease, time on hemodialysis, donor age, cold ischemia time and HLA mismatches with the group without proteinuria (n = 266). Five-year transplant survival in the group with proteinuria was 58.9% in contrast to 85.6% in recipients without proteinuria. Intermittent proteinuria did not worsen long-term prognosis. Proteinuria of 12 months or longer further reduced 5-year transplant survival to 42.6%. Over the whole observation period, serum creatinine in recipients with proteinuria was about 0.5 mg/dl higher as compared with patients without proteinuria. No correlation between proteinuria and gender, age of recipient, duration of hemodialysis, age of donor, cold ischemia time and mismatches could be detected. In conclusion, early proteinuria apparently is not due to established donor or recipient factors. However, there is a strong correlation of proteinuria with worse transplant function and survival.

Adult↗
PubMed1997

Ciguatera fish poisoning following travel to the tropics.

A 40-year-old man-as well as 15 more participants of the same meal-suddenly experienced vomiting and watery diarrhea four hours after having eaten a meal of grouper in the Dominican Republic. Symptoms persisted for four hours and were followed by a generalized pruritus and paresthesias of the lips, tongue, palms, and soles of the feet. Physical examination was normal with the exception of a pulse of 45 beats per minute, a blood pressure of 80/50 mmHg, and paradoxical temperature perception. Laboratory values were regular except for the erythrocyte sedimentation rate of 40 mm per hour. 24-hour Holter electrocardiogram showed a normal sinus rhythm with impaired heart rate variability (37-100 beats per minute). Due to the typical history and the clinical findings, ciguatera toxin ingestion was diagnosed. Pruritus decreased slightly with symptomatic therapy, but it took 16 weeks for all symptoms to resolve. Ciguatera fish poisoning is rare in temperate countries. Symptoms of this neurotoxic disease are gastrointestinal, neurologic, and cardiovascular manifestations with paresthesias, paradoxical sensor disturbances, and muscular weakness as well as bradycardia and hypotension. With travel to and from the tropics and increasing imports of tropical fish ciguatera will be of growing importance even in nontropical areas.

Adult↗
PubMed1997

Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients.

After allogenic transplantations a dramatic increase in the development of arteriosclerotic plaques can be observed, which might be due to metabolic alterations, influenced by changes of the transplant organ or immunosuppression. In this study the effects of FK 506 in kidney transplant patients on cardiovascular risk factors were compared to cyclosporin A (CsA) immunosuppression. Both groups showed no statistical differences in number, kidney function, age, body weight, sex distribution, steroid dosage and follow-up time after transplantation. Total cholesterol was similar in FK 506-treated patients (231 +/- 22 vs. 278 +/- 52 mg/dl) as compared with patients with CsA immunosuppression. Furthermore, there were no differences in triglycerides (220 +/- 72 vs. 210 +/- 67 mg/dl), HDL-cholesterol (67 +/- 14 vs. 52 +/- 18 mg/dl) and fasting glucose (112 +/- 36 vs. 116 +/- 17 mg/dl). However, the concentration of LDL-cholesterol (114 +/- 21 vs. 167 +/- 37 mg/dl), the independent risk factor Lp(a) (11 +/- 9 vs. 27 +/- 8 mg/dl) and fibrinogen (216 +/- 71 vs. 297 +/- 47) was lower in FK 506-treated patients. Our results indicate that FK 506 immunosuppression offers some advantages in cardiovascular risk factors.

Adult↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Negative chronotropic and inotropic effects exerted by diadenosine hexaphosphate (AP6A) via A1-adenosine receptors.

1. Diadenosine hexaphosphate (AP6A) exerts vasoconstrictive effects. The purpose of this study was to investigate whether AP6A has any effect on cardiac function. 2. The effects of AP6A (0.1-100 microM) on cardiac contractility and frequency were studied in guinea-pig and human isolated cardiac preparations. Furthermore, the effects of AP6A on the amplitude of the L-type calcium current, on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content and on the phosphorylation of regulatory phosphoproteins, i.e. phospholamban and troponin inhibitor, were investigated in guinea-pig isolated ventricular myocytes. 3. In isolated spontaneously beating right atria of the guinea-pig AP6A exerted a negative chronotropic effect and reduced the rate of contraction maximally by 35% (IC20 = 35 microM). 4. In isolated electrically driven left atria of the guinea-pig AP6A exerted a negative inotropic effect and reduced force of contraction maximally by 23% (IC20 = 70 microM). 5. In isolated electrically driven papillary muscles of the guinea-pig AP6A alone was ineffective, but attenuated isoprenaline-stimulated force of contraction maximally by 23% (IC20 = 60 microM). Furthermore, AP6A attenuated the relaxant effect of isoprenaline. 6. In human isolated electrically driven ventricular preparations AP6A alone was ineffective, but attenuated isoprenaline-stimulated force of contraction by maximally 42% (IC20 = 18 microM). Moreover, AP6A attenuated the relaxant effect of isoprenaline. 7. All these effects of AP6A were abolished by the selective A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX, 0.3 microM), whereas the M-cholinoceptor antagonist atropine (10 microM) and the P2-purinoceptor antagonist suramin (300 microM) failed to abolish the effects of AP6A. 8. AP6A 100 microM had no effect on the amplitude of the L-type calcium current, but attenuated isoprenaline-stimulated L-type calcium current. The maximum of the current-voltage relationship (I-V curve) was shifted to the left by isoprenaline and additional application of AP6A shifted the I-V curve back to the right to the control value. The phosphorylation state of phospholamban and the troponin inhibitor was unchanged by AP6A alone, but was markedly attenuated by AP6A in the presence of isoprenaline. Cyclic AMP levels remained unchanged by AP6A, even after stimulation with isoprenaline. 9. In summary, AP6A exerts negative chronotropic and inotropic effects in guinea-pig and human cardiac preparations. These effects are mediated via A1-adenosine receptors as all effects were sensitive to the selective A1-adenosine receptor antagonist DPCPX. Furthermore, the effects of AP6A on cyclic AMP levels, protein phosphorylation and the L-type calcium current are in accordance with stimulation of A1-adenosine receptors.

Animals↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Reduced distensibility of the common carotid artery in patients treated with ergotamine.

To investigate the effect of vascular smooth muscle contraction on mechanical vessel wall properties of proximal "elastic" arteries, we investigated the effect of the vasoconstrictor ergotamine on the distensibility of the common carotid artery in 10 migraine patients with ergotamine intake, in 10 control patients with migraine headache but no prior ergotamine intake, and in 10 healthy control subjects. The patients and control subjects were matched for age, blood pressure, and sex. In the ergotamine group, 2.2 +/- 1.4 mg ergotamine tartrate (0.25 to 6 mg) was taken within 12 hours before investigation. Differences in mean 24-hour blood pressure between the study groups were excluded by 24-hour blood pressure recording and differences in arterial wall thickness by high-resolution and differences in arterial wall thickness by high-resolution B-mode ultrasound. A multigate Doppler system was used for measurement of vessel wall movements by M-mode Doppler analysis. Blood pressure was determined by sphygmomanometry. The end-diastolic diameter of the common carotid artery was insignificantly reduced in the ergotamine group compared with the healthy control subjects and control patients (healthy control subjects, 6.6 +/- 0.4 mm; control patients, 6.7 +/- 0.5 mm; patients with ergotamine intake, 6.3 +/- 0.4 mm; P = NS). Arterial distensibility was significantly lower in the patients with ergotamine intake (17.4 +/- 4.0 10(-3)/kPa) than in the healthy control subjects (22.3 +/- 5.1 10(-3)/kPa) and control patients (22.8 +/- 3.6 10(-3)/kPa) (one-way ANOVA, P = .014). The results show that ergotamine reduces the distensibility of the common carotid artery. The data suggest that vascular smooth muscle contraction can modulate the buffering function of the arterial system independently of blood pressure changes.

Adult↗
PubMed1996

Effects of diadenosine polyphosphates on renal function and blood pressure in anesthetized Wistar rats.

In this study, the effects of diadenosine polyphosphates on kidney function were examined. Intravenous application of diadenosine hexaphosphate (AP6A) led to a significant threefold increase in both urine flow (from 2.45 +/- 0.2 to 13.8 +/- 0.74 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.41 +/- 0.12 to 1.52 +/- 0.28 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). In contrast, diadenosine triphosphate dose-dependently reduced urine flow (from 3.74 +/- 0.3 to 2.57 +/- 0.1 microL/min per 100 g body wt (P < 0.05)) and Na+ excretion (from 0.45 +/- 0.1 to 0.13 +/- 0.1 mumol/min per 100 g body wt at a dose of 1.0 mg/kg body wt). ATP and the P2y purinoceptor agonist gamma-S-ATP did not significantly modulate urine flow and Na+ excretion. alpha, beta-methylene-ATP, a P2x purinoceptor agonist, significantly increased urine flow from 1.74 +/- 0.5 to 4.07 +/- 1.51 microL/min per 100 g body wt, whereas Na+ excretion was unaffected. The effects were independent of alterations in GFR. Pretreatment with indomethacin (2.0 mg/kg body wt iv) completely abolished the effects of AP6A on urine flow and Na+ excretion. Similarly, pretreatment with the endothelin antagonist bosentan abolished the effects of AP6A on both urine flow and Na+ excretion, whereas suramin had no effects on the AP6A-induced increase in urine flow. In conclusion, diadenosine polyphosphates exert specific actions on urine flow and Na+ excretion that are different from the effects of ATP. AP6A may partially influence renal function by stimulating prostaglandin and endothelin release.

Anesthesia↗