Metals (Ag+, Cd2+, Cr6+) affect ATPase activity in the gill,kidney, and muscle of freshwater fish Oreochromis niloticus following acute and chronic exposures

Freshwater fish Oreochromis niloticus were individually acutely exposed to different concentrations (0, 0.1, 0.5, 1.0, and 1.5 μg/mL) of Cd²⁺, Cr⁶⁺, and Ag⁺ for 96 h and 0.05 μg/mL concentration of the same metals for different periods (0, 5, 10, 20, and 30 days) chronically. Following each experimental protocol, Na⁺/K⁺‐ATPase, Mg²⁺‐ATPase, and Ca²⁺‐ATPase activities were measured in the gill, kidney, and muscle of O. niloticus. In vitro experiments were also performed to determine the direct effects of metal ions (0, 0.1, 0.5, 1.0, and 1.5 μg/mL) on ATPases. Except Ag⁺, none of the metals caused fish mortality within 30 days. Silver killed all the fishes within 16 days. Metal exposures generally decreased Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase activities in the tissues of O. niloticus, although there were some fluctuations in Mg²⁺‐ATPase activity. Ag⁺ and Cd²⁺ were found to be more toxic to ATPase activities than Cr⁶⁺. It was also observed that metal efficiency was higher in the gill than in the other tissues. Results indicated that the response of ATPases varied depending on metals, exposure types, and tissues. Because ATPases are sensitive to metal toxicity, their activity can give valuable data about fish physiology. Therefore, they may be used as a sensitive biomarker in environmental monitoring in contaminated waters. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 707–717, 2013.     

Effects of Methyl Mercury and Triethyllead on Na+K+ATPase and Pyruvate Dehydrogenase Activities in Glioma C6 Cells

Abstract: The effect of methyl mercury (MeHg) and triethyllead (Et₃Pb) on the membrane bound SH-enzymes Na⁺K⁺ATPase and pyruvate dehydrogenase (PDH) was studied in relation to the effect on the galactosyl ceramide sulfotransferase (CST) and to morphological changes in glioma C₆ cells. Two-day-old cultures were incubated for 1 or 20 hrs with 5–30 μg MeHgCl and 2–8 μg Et₃PbCl/mg cell protein. The results show that both compounds induced morphological changes and a reduction of CST activity at growth inhibitory concentrations. A less marked reduction of Na⁺K⁺ATPase was induced with increasing exposure time only in MeHgCl treated cultures, and PDH activity was not affected by either of the compounds under the experimental conditions. Thus, an interference with Na⁺K⁺ATPase and PDH activities do not appear to be a primary effect of MeHg and Et₃Pb intoxication.     

Diverging Effects of 5‐HT3 Receptor Antagonists Ondansetron and Granisetron on Estramustine‐Inhibited Cellular Potassium Transport

Abstract: We used ⁸⁶Rb⁺ (K⁺ analogue) to study potassium influx during the interaction of highly specific 5‐HT₃‐receptor antagonists, ondansetron and granisetron, with the effects of the anticancer drug, estramustine phosphate, on P31 mesothelioma cells. Estramustine phosphate (80 mg/l, 142 μmol/l) for 120 min. reduced ⁸⁶Rb⁺ influx by 18.7%. The reduction was inhibited by ondansetron (0.1 μmol/l), but augmented by granisetron (0.1 μmol/l). Serotonin (1.0 μmol/l) antagonized ondansetron inhibition and restored granisetron‐augmented reduction of estramustine phosphate‐induced ⁸⁶Rb⁺ influx to the level of the drug itself. Estramustine phosphate inhibited cellular Na⁺, K⁺, 2Cl^? ‐cotransport activity whereas Na⁺, K⁺, ATPase activity was unaffected. Ondansetron blockade of estramustine phosphate‐induced reduction of ⁸⁶Rb⁺ influx was due to increased Na⁺, K⁺, ATPase and Na⁺, K⁺, 2Cl^?‐cotransport whereas augmentation of estramustine phosphate‐induced reduction of ⁸⁶Rb⁺ influx by granisetron, or combination of 5‐HT₃ receptor antagonists with serotonin was due mainly to inhibition of cellular Na⁺, K⁺, ATPase activity. Thus, ondansetron possesses a distinct ability to reverse K⁺ influx of tumour cells exposed to estramustine phosphate whereas granisetron does not, due to different effect on cellular Na⁺, K⁺, ATPase and Na⁺, K⁺, 2Cl^? ‐cotransport activity. Highly 5‐HT₃ receptor‐specific antiemetic agents may have different effects on ion transport of tumour cells during treatment with cytotoxic drugs.     

Physiological and molecular responses in brain of juvenile common carp (Cyprinus carpio) following exposure to tributyltin

Tributyltin (TBT), as antifouling paints, is widely present in aquatic environment, but little is known regarding the toxicity of TBT on fish brain. In this study, the effects of exposure to TBT on the antioxidant defense system, Na⁺‐K⁺‐ATPase activity, neurological enzymes activity and Hsp 70 protein level in brain of juvenile common carp (Cyprinus carpio) were studied. Fish were exposed to sublethal concentrations of TBT (5, 10 and 20 μg/L) for 7 days. Based on the results, with increasing concentrations of TBT, oxidative stress was apparent as reflected by the significant higher levels of oxidative indices, as well as the significant inhibition of all antioxidant enzymes activities. Besides, the activities of Acetylcholinesterase (AChE), Monoamine oxidases (MAO) and Na⁺‐K⁺‐ATPase were significantly inhibited after exposure to TBT with higher concentrations. In addition, the levels of Hsp 70 protein were evaluated under TBT stress with dose‐depended manner. These results suggest that selected physiological responses in fish brain could be used as potential biomarkers for monitoring residual organotin compounds present in aquatic environment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 278–284, 2016.     

Advanced glycation end‐products impair Na+/K+‐ATPase activity in diabetic cardiomyopathy: Role of the adenosine monophosphate‐activated protein kinase/sirtuin 1 pathway

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Chronic exposure to dichloroacetamide induces biochemical and histopathological changes in the gills of zebrafish

To evaluate the impact of DCAcAm on zebrafish gill, we measure the responses of antioxidant enzyme (superoxide dismutase, SOD), lipid peroxidation (malondialdehyde, MDA), ATPase (Na⁺/K⁺‐ATPase and Ca²⁺/Mg²⁺‐ATP) and histopathological changes of gill in adult zebrafish, after exposed to different concentrations of DCAcAm (0, 1, 10, 100, and 1000 μg L^?1) for 30 days. Results indicated that DCAcAm first increased and then decreased SOD activity, and DCAcAm also lowered the activities of Na⁺/K⁺‐ATPase and Ca²⁺/Mg²⁺‐ATPase. These results indicated that high affinity of DCAcAm probably be a main factor, which can damage the structures of enzymes, thereby inhibiting the SOD and ATPase activities. Besides, histopathological investigation results also manifested that chronic exposure to DCAcAm can damage the gill tissues, disrupting the normal function of gills. We conclude that chronic exposure to DCAcAm was harmful to organisms, not only influence gill function, but also further cause damage on the gill tissues.     

Effects of adrenochrome on rat heart sarcolemmal ATPase activities

Effects of adrenochrome on rat heart sarcolemmal ATPase, calcium binding and adenylate cyclase activities were studied _vitro. Adrenochrome (1–100 μg/ml) did not affect calcium binding activity. Significant decreases in adenylate cyclase and Ca²⁺ ATPase activities were seen only at a concentration of 100 μg/ml adrenochrome. Adrenochrome depressed Na⁺?K⁺ ATPase activity in a dose-dependent manner. The inhibitory effect on Na⁺?K⁺ ATPase of adrenochrome was also observed in sarcolemmal membranes washed with a buffer after treatment with adrenochrome. The percentage inhibition of the enzyme activity was independent over a wide range of pH (6.6–7.8) and concentrations of NaCl/KCl (40/4–100/10,mM/mM). A study on the combined effects of adrenochrome and either ouabain or CaCl₂ showed that, unlike ouabain, calcium produced additive inhibition with adrenochrome. Depression of Na⁺?K⁺ ATPase activity was also observed in sarcolemma isolated from the heart perfused with adrenochrome. Since adrenochrome has been demonstrated to produce myocardial cell damage and contractile failure in the perfused heart, the present experiments provide a possible explanation for the genesis of adrenochrome-induced cardiotoxicity.     

Subchronic exposure to diflubenzuron causes health disorders in neotropical freshwater fish,Prochilodus lineatus

The action of diflubenzuron (DFB) was evaluated in a freshwater fish, Prochilodus lineatus, after exposure to 0.06, 0.12, 0.25, or 0.50 mg L^?1 DFB for 14 days. Erythrocyte nuclear abnormalities (ENA), the gill activity of Na⁺/K⁺‐ATPase, H⁺‐ATPase and carbonic anhydrase (CA), and lipid peroxidation (LPO) and histopathological changes in the gills and liver were determined. The number of micronuclei increased in fish exposed to 0.25 and 0.50 mg L^?1 DFB. Plasma Cl^? and the CA activity decreased, while the activity of Na⁺/K⁺‐ATPase and of H⁺‐ATPase increased in fish exposed to 0.25 and 0.50 mg L^?1 DFB. LPO did not change in the gills but increased in the liver of fish exposed to 0.25 and 0.50 mg L^?1 DFB. In the gills, histopathological changes indicated disperse lesions and slight to moderate damage in fish exposed to 0.50 mg L^?1 DFB, whereas in the liver, these changes were significantly greater in fish exposed to 0.25 and 0.50 mg L^?1 DFB, indicating moderate to severe damage. Continuous exposure to DFB is potentially toxic to P. lineatus, causing heath disorders when the fish is exposed to the two highest DFB concentrations, which are applied to control parasites in aquaculture and to control mosquito populations in the environment. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 533–542, 2016.     

Effects of cadmium alone and in combination with low molecular weight chitosan on metallothionein,glutathione‐S‐transferase,acid phosphatase,and ATPase of freshwater crab Sinopotamon yangtsekiense

Cadmium (Cd) is an environmental contaminant showing a variety of deleterious effects, including the potential threat for the ecological environment and human health via food chains. Low molecular weight chitosan (LMWC) has been demonstrated to be an effective antioxidant. Metallothionein (MT) mRNA levels and activities of glutathione‐S‐transferase (GST), superoxide dismutase (SOD), acid phosphatase (ACP), Na⁺,K⁺‐ATPase, and Ca²⁺‐ATPase as well as malondialdehyde (MDA) contents in the gills of the freshwater crab Sinopotamon yangtsekiense were analyzed in vivo in order to determine the injury of Cd exposure on the gill tissues as well as the protective effect of LMWC against this injury. The results showed that there was an apparent accumulation of Cd in the gills, which was lessened by the presence of LMWC. Moreover, Cd²⁺ significantly increased the gill MT mRNA levels, ACP activity and MDA content while decreasing the activities of SOD, GST, Na⁺,K⁺‐ATPase, and Ca²⁺‐ATPase in the crabs relative to the control. Cotreatment with LMWC reduced the levels of MT mRNA and ACP but raised the activities of GST, Na⁺,K⁺‐ATPase, and Ca²⁺‐ATPase in gill tissues compared with the crabs exposed to Cd²⁺ alone. These results suggest that LMWC may exert its protective effect through chelating Cd²⁺ to form LMWC‐Cd²⁺ complex, elevating the antioxidative activities of GST, Na⁺,K⁺‐ATPase, and Ca²⁺‐ATPase as well as alleviating the stress pressure on MT and ACP, consequently protecting the cell from the adverse effects of Cd. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 298–309, 2014.     

Effects of soluble copper and copper oxide nanoparticle exposure on the immune system of mussels,Mytilus galloprovincialis

Copper and copper oxide nanomaterials (nCuO) can enter the marine environment negatively impacting mussels, an environmental and commercially relevant organism. We analyzed the effects on the immune system of adult mussels exposed to soluble copper (CuSO₄, 20‐50 μg/L) or nCuO (100‐450 μg/L). CuSO₄ caused significant copper accumulation in gills and cell‐free hemolymph, while nCuO caused cell damage to gills and significant copper accumulation in hemocytes, the most abundant cells in the hemolymph. Both sources of copper caused cellular toxicity in hemocytes by increasing reactive oxygen species production and lysosome abundance, and decreasing multi‐drug resistance transporter activity. Though hemocyte abundance was not affected, their in‐vitro phagocytic activity decreased, explaining the slight (but not statistically significant) increase in bacterial proliferation in mussels exposed to the pathogenic bacteria Vibrio tubiashii following copper exposure. Thus, exposure to non‐lethal concentrations of CuSO₄ or nCuO can potentially increase mussel susceptibility to bacterial infections.     

Biochemical biomarkers in liver and gill tissues of freshwater fish Carassius auratus following in vivo exposure to hexabromobenzene

Hexabromobenzene (HBB) is a novel brominated flame retardant (BFR) with ample evidence of its ubiquitous existence in the aquatic ecosystems. However, to date, the toxicological effects of this BFR on fish have been inadequately researched. The present study was conducted, based on an in vivo model, to investigate HBB‐induced biochemical changes in liver and gill tissues of Carassius auratus after medium‐term exposure to different concentrations (10, 150, and 300 mg/kg) for 7, 14, and 25 days. Oxidative stress was evoked evidently for the prolonged exposure, demonstrated by significant inhibition in antioxidant enzymes activities including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S‐transferase, and a decrease in reduced glutathione level, as well as simultaneous elevation in malondialdehyde content. Moreover, Na⁺, K⁺‐ATPase activity, and protein level were remarkably reduced in fish tissues. Based on the integrated biomarker response, the toxic potency in each treatment was distinguished, and the more severe stress was mainly noted with the increasing concentrations and the extending durations. It was also observed that liver exhibited more pronounced alterations in biochemical parameters than gill, probably indicating the vulnerability of liver to HBB‐triggered oxidative stress. Taken together, the results of this study clearly showed that HBB was capable of inducing oxidative stress and inhibiting Na⁺, K⁺‐ATPase activity in different tissues of C. auratus after medium‐term exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1460–1470, 2014.     

Targeting Na+/K+‐translocating adenosine triphosphatase in cancer treatment

The Na⁺/K⁺‐translocating adenosine triphosphatase (ATPase) transports sodium and potassium across the plasma membrane and represents a potential target in cancer chemotherapy. Na⁺/K⁺‐ATPase belongs to the P‐type ATPase family (also known as E1–E2 ATPase), which is involved in transporting certain ions, metals, and lipids across the plasma membrane of mammalian cells. In humans, the Na⁺/K⁺‐ATPase is a binary complex of an α‐subunit that has four isoforms (α₁–α₄) and a β‐subunit that has three isoforms (β₁–β₃). This review aims to update our knowledge on the role of Na⁺/K⁺‐ATPase in cancer development and metastasis, as well as on how Na⁺/K⁺‐ATPase inhibitors kill tumour cells. The Na⁺/K⁺‐ATPase has been found to be associated with cancer initiation, growth, development, and metastasis. Cardiac glycosides have exhibited anticancer effects in cell‐based and mouse studies via inhibition of the Na⁺/K⁺‐ATPase and other mechanisms. Na⁺/K⁺‐ATPase inhibitors may kill cancer cells via induction of apoptosis and autophagy, radical oxygen species production, and cell cycle arrest. They also modulate multiple signalling pathways that regulate cancer cell survival and death, which contributes to their antiproliferative activities in cancer cells. The clinical evidence supporting the use of Na⁺/K⁺‐ATPase inhibitors as anticancer drugs is weak. Several phase I and phase II clinical trials with digoxin, Anvirzel, and huachansu (an intravenous formulated extract of the venom of the wild toad), either alone or more often in combination with other anticancer agents, have shown acceptable safety profiles but limited efficacy in cancer patients. Well‐designed randomized clinical trials with reasonable sample sizes are certainly warranted to confirm the efficacy and safety of cardiac glycosides for the treatment of cancer.     

Graphene oxide quantum dot exposure induces abnormalities in locomotor activities and mechanisms in zebrafish (Danio rerio)

Graphene oxide quantum dots (GOQDs) have broad applications such as bioimaging and drug delivery, among others, even expanding into the aquatic environment. However, reports on the adverse effects of GOQDs on fish development are limited. In this study, we exposed zebrafish embryos to GOQDs for 7 days after fertilization and found that GOQDs exposure at low concentrations (12.5, 25, 50 or 100 μg/L) decreased the total distance and the mean velocity of larvae movement. Additionally, the GOQDs significantly reduced the enzyme activity related to energy supply and locomotor capacity, including Ca²⁺-ATPase in the 12.5, 25, 50 and 100 μg/L GOQDs groups and Na⁺/K⁺-ATPase in the 25 and 50 μg/L GOQDs groups. Moreover, GOQD exposure altered the mRNA expression of genes involved in energy supply and calcium transport. The levels of the atp2a2b, atp2a1, and cacna1sb genes were significantly downregulated in the 25, 50 and 100 μg/L GOQDs groups, and ryr3 expression was significantly reduced in the 25 and 50 μg/L GOQDs groups. The expression level of cacna1c was significantly upregulated in the 50 and 100 μg/L GOQDs groups. In summary, GOQD exposure induced a decrease in locomotor capacity in zebrafish, which may be due to the reduction of Ca²⁺-ATPase and Na⁺/K⁺-ATPase activity levels, and dysregulated expression of the genes involved in energy metabolism and calcium transport. Our study provides novel insight into the effects of GOQDs on the embryonic development of fish, which will be useful for the development of environment-friendly GOQDs that reduce the potential hazard to aquatic species.     

Comparative effects of substituted phenothiazines and their free radicals on (Na =, K + )-activated adenosine triphosphatase

The inhibitory effects of free radicals of various substituted phenothiazines on (Na⁺,K⁺)-activated ATPase [Mg²⁺-dependent, (Na⁺,K⁺)-activated ATP phosphohydrolase; EC 3.6.1.3] were studied in vitro. Enzyme preparations were obtained from rat brain microsomal fractions after deoxycholic acid and NaI treatments. Free radicals were produced by either ultraviolet (253.7 nm) irradiation or enzymatic oxidation with peroxidase. Without enzymatic or photo-oxidation, phenothiazine derivatives failed to inhibit (Na⁺,K⁺)-activated ATPase activity significantly. Photo-oxidative intermediates of thioridazine, triflupromazine and trifluoperazine were potent inhibitors of (Na⁺,K⁺)-activated ATPase activity. Those from chlorpromazine, perphenazine and promazine were less potent. Peroxidase-hydrogen peroxide treatment of promazine, thioridazine, perphenazine and chlorpromazine produced free radical intermediates which significantly inhibited (Na⁺,K⁺)-activated ATPase activity. The same treatment of triflupromazine and trifluoperazine, however, failed to produce detectable amounts of free radical intermediates. Concomitantly, no inhibition of (Na⁺,K⁺)-activated ATPase activity was observed under these conditions. It was concluded that free radical intermediates of various substituted phenothiazines are differentially potent inhibitors of (Na⁺,K⁺)-activated ATPase, and that the formation of free radicals from substituted phenothiazines is dependent upon the oxidizing conditions and nature of substituent groups.     

High doses of 2,2′‐dithienyl diselenide cause systemic toxicity in rats: an in vitro and in vivo study

Organoselenium compounds have important pharmacological properties. However, these compounds can cause toxicity, typically related to oxidation of endogenous thiols. The aim of this study was to investigate whether 2,2′‐dithienyl diselenide (DTDS) has potential toxicity in vitro and in vivo. Therefore, sulfhydryl‐containing enzyme activities, δ‐aminolevulinic acid dehydratase (δ‐ALA‐D) and Na⁺–K⁺‐ATPase were used to predict DTDS toxicity in rat brain homogenate in vitro. In in vivo experiments, a DTDS administration (50 or 100 mg kg^?1, p.o.) to rats was performed and toxicological parameters were determined. DTDS inhibited δ‐ALA‐D (IC₅₀ 2 µm ) and Na⁺–K⁺‐ATPase (IC₅₀ 17 µm ) activities in vitro. The inhibitory effect of DTDS on δ‐ALA‐D and Na⁺–K⁺‐ATPase activities was restored by dithiothreitol. DTDS (5–25 µm ) elicited a thiol oxidase‐like activity. In vivo, DTDS (50 and 100 mg kg^?1) caused systemic toxicity, evidenced by a decrease in water and food intakes and body weight gain, as well as the death of rats. DTDS at the dose of 100 mg kg^?1 increased plasma alanine and aspartate aminotransferase activities and decreased urea levels. At 50 and 100 mg kg^?1, it increased lipid peroxidation levels. At the highest dose, DTDS inhibited δ‐ALA‐D activity. By contrast, Na⁺–K⁺‐ATPase activity and antioxidant defense were not altered in the brains of rats exposed to DTDS. In conclusion, interaction with the cisteinyl residues seems to mediate the inhibitory effect of DTDS on sulfhydryl‐containing enzymes in vitro. In addition, high oral doses of DTDS induce toxicity in rats. Copyright © 2011 John Wiley & Sons, Ltd.     

Effect of ethanol and acetaldehyde on the (Na+ +K+)-activated adenosine triphosphatase activity of cardiac plasma membranes.

Ethanol and acetaldehyde inhibited the (Na⁺ + K⁺)-activated ATPase activity of plasma membranes prepared from the guinea-pig heart. The degree of inhibition was dose-dependent and antagonized by the K⁺ concentration in the reaction mixture. The inhibition is not attributable to increase in osmolality. The presence of ethanol or acetaldehyde in the reaction mixture was necessary for the inhibitory effect. Plasma membranes treated with ethanol or acetaldehyde and subsequently washed showed no impairment of (Na⁺ + K⁺)-activated ATPase activity. Prolonged exposure of the plasma membranes to a low concentration of ethanol was ineffective in increasing the inhibition of ATPase activity.     

Micro-colorimetric determination of adenosinetriphosphatase activity in freeze-dried sections of rat diaphragm muscle

A technique is described for determination of ATPase activity in 3–30 μg samples dissected from freeze-dried sections of rat diaphragm muscle. Tissue samples are incubated at room temperature with optimal concentrations of ATP (10 mM) and MgSO₄ (5 mM) in 0·1 M tris/HCl buffer at pH 7·4. Inorganic phosphate is measured spectrophotometrically. Mean activity for 20 rats was 0·22 ± 0·06 (s.d.) mole-Pi/kg/wet tissue/15 min. Results did not depend on plane of section or section thickness. 5 mM Mg²⁺, 10 mM Ca²⁺ and 1 mM 2, 4-dinitrophenol produced maximal ATPase activation and inhibition was obtained with p-chloromercuribenzoic acid (pI₅₀3·9) but not chlorpromazine (0·01–0·1 mM). There was no significant evidence of Na⁺ plus K⁺ activated ATPase or inhibition with ouabain (5 mM). ATPase activity was uncharacterized and relative contributions of specified muscle ATPase systems were unknown. As an insoluble enzyme system was involved and photomicrographs showed characteristic muscle features in freeze-dried sections, ATPase activity appeared due to enzymic function in situ. Results are discussed in relation to mutual availability of enzymic sites and reagents.     

The Influence of Potassium Concentration on the Inhibitory Effect of Amiodarone on Guinea-Pig Microsomal Na+-K+-ATPase Activity

Abstract: The effects of varying incubation K⁺ concentration on the inhibitory action of amiodarone on the Mg²⁺-dependent ATP hydrolysis by myocardial Na⁺-K⁺-ATPase (EC 3.6.1.3) were studied in guinea pig heart preparations. In the first part of the study, it was established that the activity of the enzyme increased with growing concentrations up to approximately 20 mM K⁺. The concentration-response relationships for amiodarone were investigated in incubation media containing 2.5, 5.0 and 10 mM K⁺ respectively. Amiodarone exhibited similar concentration-dependent inhibitory effects in the range of 0.01 nM ?80 μM at 2.5 mM, 0.13–150 μM at 5.0 mM and 0.3–700 μM at 10.0 mM K⁺. The corresponding IC50 values were 10.4 ± 3.2 μM at 2.5 mM, 28.3 ± 7.6 μM at 5.0 mM and 33.3 ± 9.2 μM at 10.0 mM K⁺, respectively. Thus, reduction in the K⁺ concentration from the “standard” 5.0 to 2.5 mM was accompanied by a significant right-to-left shift in the inhibitory potency of amiodarone, the effective concentrations being shifted from uM into nM ranges. Increasing K⁺ concentration to 10 mM on the other hand attained opposite but less remarkable effects. The results show that the in vitro inhibition of myocardial Na⁺-K⁺-ATPase activity by amiodarone is related to the K⁺ concentration of the incubation medium. These effects may be pertinent to the mechanism by which this drug interferes with the electrogenic Na⁺/K⁺ pump activity of the enzyme, thereby probably contributing to the mechanism(s) responsible for some of its cardiac actions.     

Stimulation of Na+,K+-ATPase of isolated smooth muscle membranes by the Ca2+ channel inhibitors,nimodipine and nitrendipine

Nimodipine (0.015 to 1.5 μM) increased Na⁺, K⁺-ATPase activity by 70–120% in isolated smooth muscle membranes. At 0.015 μM, nitrendipine, but not nifedipine, verapamil or diltiazem, also activated this enzyme. Nimodipine stimulated this Na⁺, K⁺ATPase three times more than nitrendipine at 15 nM. Marked stimulation of Na⁺,K⁺-ATPase by nimopidine was seen in membranes from rat and guinea pig aorta and rat vas deferens, but not in membranes from guinea pig heart or brain. Although it is not known whether these results are applicable to intact cells, the results are consistent with the hypothesis that vasodilation produced by nimodipine and nitrendipine may be due not only to inhibition of Ca²⁺ entry but also to the stimulation of the Na^? pump.     

Impaired participation of potassium channels and Na+/K+‐ATPase in vasodilatation due to reduced nitric oxide bioavailability in rats exposed to mercury

Mercury intoxication is a public health risk factor due to its hazardous effect to several organs, including the cardiovascular system. There is evidence of endothelial dysfunction after exposure to mercury, but the effects on endothelium‐dependent vasodilatation are still unknown. In the present study, we aimed to evaluate the chronic effects of high HgCl₂ doses on the mechanisms of vasodilatation. Wistar rats were injected with HgCl₂ (1st dose 10.86 μg/kg, and daily doses 0.014 μg/kg for 30 days i.m.), and saline was used as control. Mercury exposure reduced the acetylcholine‐induced vasodilatation in aortic rings, which was restored by incubation with antioxidant tiron. Inhibition of the NO synthase, Na⁺/K⁺‐ATPase and K⁺ channels indicates reduced participation of these factors. In the mercury group, there were an increased local anion superoxide and a reduced NO. The vasodilatation to exogenous NO was partially inhibited by co‐incubation with TEA plus tiron, suggesting that reduced NO bioavailability is the responsible to that decreased the participation of K⁺ channels. Moreover, there was an increased participation of the Na⁺/K⁺‐ATPase associated with an up‐regulation of its alpha‐1 subunit. In conclusion, reduced NO bioavailability plays a major role in the impaired participation of K⁺ channels and Na⁺/K⁺‐ATPase in the acetylcholine‐mediated relaxation, although sodium pump is up‐regulated probably as a compensatory mechanism.