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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 163 (1989), S. 458-465 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Cyclosporine ; Calcium ; Vascular smooth muscle ; Mesangial cells ; Atrial natriuretic peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunosuppressive therapy with cyclosporine A (CyA) may be associated with severe side effects such as nephrotoxicity and arterial hypertension. The partial reversibility of these effects suggests that they are at least in part functional. The present study examined the effects of CyA on cellular signaling in vascular smooth muscle cells and in glomerular mesangial cells and the interactions with the endogenous vasodilator atrial natriuretic peptide (ANP). Intracellular free calcium concentrations ([Ca2+]i) were measured using Fura-2. 45Ca2+ was used to measure Ca2+ efflux and cellular Ca2+ influx. In the presence of cyclosporine (10 μg/ml), the Ca2+-mobilizing effects of angiotensin II (10−8 M) in smooth muscle cells and of arginine vasopressin (AVP) in mesangial cells were significantly enhanced. CyA significantly stimulated cellular Ca2+ uptake in both cell types. ANP blocked the Ca2+ mobilization by angiotensin II and AVP and also completely inhibited the potentiating effect of CyA on angiotensin II- and AVP-induced Ca2+ mobilization. ANP also completely blocked the CyA-stimulated Ca2+ uptake. These findings suggest that CyA stimulates transmembrane Ca2+ influx, thereby increasing vasopressor-sensitive intracellular Ca2+ stores and augmenting vasopressor-induced Ca2+ mobilization. This cellular effect of CyA in vitro was markedly diminished by ANP. The effects of CyA on intracellular signaling may directly enhance the contractile response of smooth muscle and the glomerular mesangium to vasopressor stimuli and may also contribute to other disturbances of cell metabolism associated with CyA.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 69 (1991), S. 841-841 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: ANP ; Renal failure ; Hemodynamics ; Renal function ; Sodium homeostasis ; Renin-aldosterone-axis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the effects of 60 minα-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m2 and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6±9.1 vs 13.6±1.9 pmol/l,p〈0.05; cGMP: 14.3±2.9 vs 6.6±1.1 pmol/ml,p〈0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5±3.2 vs. 17.3±1.3 pmol/ml,p〈0.05). During ANP infusion, GFR increased in CRF by 70.7±4.2% from 34.5±6.8 to 57.4±9.9 ml/min/1.73m2 (p〈0.001) as compared to 16.2±1.4% in C (p〈0.001 vs CRF). RBF increased in CRF by 43.6±6.4% and in C by 3.1±1.2% (p〈0.01). Basal urinary sodium excretion (UNaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, UNaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FENa), however, was more pronounced in C. Basal FENa was higher in CRF (12.8±2.5% vs 2.4±1.5% in C,p〈0.001), FENa remained elevated at 180% over baseline in C sixty minutes after cessation of ANP infusion, while it had returned to baseline in CRF. During ANP infusion, CI increased in CRF after 30 min from 2.91±0.08 to 3.12±0.091/min/m2 (p〈0.001) and in C from 3.20±0.11 to 3.39±0.13 l/min/m2 (p〈 0.05). Mean arterial BP was higher in CRF and its decrease was greater than in C (21.1±2.7% vs 9.1±1.0%,p〈0.001). In patients with CRF GFR, RPF, and CI remained significantly elevated and BP was still significantly decreased 60 min after ANP infusion. Total peripheral vascular resistance (TPR) was elevated in CRF and declined during ANP infusion in both CRF and C. The decline of TPR was sustained and more pronounced in CRF than in C. Renal vascular resistance (RVR) was high in CRF and dropped by nearly 50% during ANP infusion, whereas only a moderate decline in RVR during ANP application was observed in C. Thus, exogenous ANP had greater and prolonged effects on systemic hemodynamics and renal function in CRF than in C. They may be due to higher levels of ANP following ANP infusion and appear to be mediated by a more sustained formation of the second messenger cGMP.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 69 (1991), S. 942-942 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1440
    Keywords: Cyclosporine ; Calcium ; Na-KATPase ; Vascular smooth muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of cyclosporine A in enhancing vasconstrictor-induced calcium (Ca2+) mobilization in vascular smooth muscle cells may contribute to important side effects in cyclosporine therapy such as hypertension and nephrotoxicity. As we have previously shown, cyclosporine A stimulates transmembrane Ca2+ influx. Since Ca2+ efflux was not affected by cyclosporine A, we concluded that cyclosporine augments angiotensin II induced Ca2+ mobilization in vascular smooth muscle cells by an increased amount of Ca2+ in angiotensin II sensitive intracellular Ca2+ stores. The present study was therefore designed to examine the effect of cyclosporine A on cellular calcium content and on membrane calcium transport mechanisms. An important mechanism of Ca2+ extrusion from the cell is the Na-Ca exchanger. Its activity is closely related with that of the Na-ATPase. By increasing cellular sodium concentration the blockade of Na-ATPase would in turn activate cellular calcium uptake bx the Na-Ca exchanger. Therefore, we hypothesized that cyclosporine A might exert its effects in the same manner as a circulating Na-ATPase inhibitor. Total cell calcium was measured by atomic absorption and activity of Na-ATPase was estimated by an assay measuring phosphate production. Preincubation of the cells with cyclosporine (10 μg/ml) for 15 min increased total cell calcium from 31.4 ± 5.0 to 46.5 ± 5.3 nmol/mg protein (P 〈 0.05). Activity of Na-ATPase was not affected by cyclosporine A (3.9 ± 0.2 vs. 4.3 ± 0.2 μol Pi h−1 mg−1 protein). Therefore, cyclosporine A induced Ca2+ influx is not mediated by an inhibition of the Na-ATPase. Cyclosporine-stimulated accumulation of cellular calcium may be mediated, for example, by opening of calcium channels in the plasma membrane. Increased Ca2+ mobilization in the presence of cyclosporine A may be due to an increased amount of Ca2+ avaible from intracellular Ca2+ stores. These results are of substantial significance for understanding the pathophysiological mechanisms of cyclosporine A induced vasoconstriction.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 1112-1118 
    ISSN: 1432-1440
    Keywords: Atrial natriuretic peptide (ANP) ; Intracellular calcium ; Natriuretic hormone ; Ouabain-like factor (OLF) ; Vascular smooth muscle cell (VSMC) ; Platelets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The existence of an endogenous natriuretic hormone and ouabain-like factors (OLF) has been postulated for many years. This postulate was based on our original observation that a small M.W. fraction in the serum after acute expansion of the extracellular fluid volume (ECFV) not only exhibited natriuretic activity but also inhibited the Na-K-ATPase enzyme in vitro similar to ouabain. Since then, numerous studies confirmed the presence of OLFs in serum, urine, cerebrospinal fluid, and various organs including the heart and hypothalamus. Some of these OLFs are well-known endogenous compounds, such as free unsaturated fatty acids, which inhibit in vitro transmembranous sodium transport, Na-K-ATPase and3H-ouabain binding to its membrane receptor or crossreact with digoxin antibodies. Chemically yet undefined OLFs of potentially hypothalamic origin were detected in various models of experimental and clinical hypertension and are suggested to play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs isolated from the urine of salt-loaded healthy subjects strongly enhance basal and vasopressin-stimulated release of calcium in vascular smooth muscle cells and platelets similar to the effects we had observed with endothelin. This urine fraction also exhibits natriuretic activity which increases in parallel with sodium intake. Further chromatographic separation and amino acid analysis confirmed the peptidic nature (M.W.〈1000) of the natriuretic factor(s). However, the two biological activities, namely natriuretic and ouabain-like activities, reside in distinct and chemically different compounds. In face of the previous discovery of the atrial natriuretic peptides (ANP) it is of special interest that very recent observations strongly suggest a natriuretic factor of non-cardiac origin to play an important role in the natriuresis that follows ECFV expansion. In addition, numerous experimental data point to an interaction between the ANP and OLF systems. They should stimulate once again the final identification of these yet unknown endogenous natriuretic and ouabain-like factors.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 69 (1991), S. 797-801 
    ISSN: 1432-1440
    Keywords: Hypokalemia ; Oral potassium substitution ; Acid-Base Status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an open, randomized study, we investigated the effect of oral potassium chloride (KCl) and of potassium citrate/bicarbonate (K-cit/bic) in 42 patients with hypokalemia (≤3.5 mmol/l). In both groups 80 mmol K+ were administered daily. The parameters examined were serum potassium concentration, acid-base status, and urinary electrolyte excretion. Parameters were evaluated on days 0, 2, 4, and 6. With KCl, [K+] increased from 3.2± 0.2 (mean± SD) on day 0 to 3.8± 0.4 mmol/l on day 2 (p〈0.005) and 4.0± 0.5 mmol/l on day 4 (p〈 0.005). On day 6 [K+] was also 4.0±0.4 mmol/l (p〈 0.005 vs day 0). With K-cit/bic, [K+] increased from 3.2± 0.2 to 3.7± 0.4 on day 2, 3.9± 0.5 on day 4, and 4.1± 0.6 mmol/l on day 6 (allp〈 0.005 vs day 0). The increase of [K+] was not different between the two groups. Blood pH on day 0 was in the normal range in both groups and did not change significantly during the study. There was a decrease of carbon dioxide partial pressure (pCO2) with KCl from 38.7± 4.9 on day 0 to 36.4± 3.6 on day 2 (p〈0.05). On days 4 and 6, pCO2 was back up to the basal level. In contrast, with K-cit/bic, pCO2 rose from 35.0±5.8 mmHg on day 0 to 39.9± 5.8 mmHg on day 2 (p〈 0.05). On days 4 and 6, pCO2 was not different from day 0. The increase in urinary potassium excretion was equal in both groups. These results indicate that oral substitution with either KCl or K-citrate/bicarbonate may have only minor effects on the acid-base status under the conditions of the present study. Both potassium salts appeared to be equally effective in correcting hypokalemia via the oral route.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 72 (1994), S. 703-705 
    ISSN: 1432-1440
    Keywords: Atrial natriuretic peptide ; Endothelin ; Renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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