Sodium-potassium Adenosine Triphosphatase Activity Research Articles

Pathogenesis and Treatment of Refractory Oedema in Nephrotic Syndrome

Oedema is a hallmark feature of nephrotic syndrome (NS) and can cause significant patient morbidity. The pathogenesis of oedema formation is complex and results from abnormalities in sodium retention, inter-play of neurohormonal factors, and changes in capillary filtration barrier. Salt retention is often primary (‘overfill’ theory) because of increased sodium-potassium adenosine triphosphatase activity in the collecting duct cells, increased direct epithelial sodium channel activation (ENaC) by urinary proteases (independent of aldosterone), and an overall increased effective arterial blood volume. However, a subset of patients with NS, especially children, demonstrate decreased effective arterial blood volume (‘underfill’ theory) and secondary sodium retention as the primary mechanism of oedema formation. Increased capillary permeability and vascular inflammation contributes as well. Loop diuretics with or without salt-poor albumin are the mainstay of therapy in adults, although no large clinical trials exist to guide diuretic choice or dosage. Combination diuretic therapy is recommended to achieve multi-site nephron blockade and overcome diuretic resistance, which is a frequent challenge. Use of direct ENaC inhibitors (amiloride) in combination with loop diuretics may be especially beneficial given the primary role of ENaC in sodium retention. Aquaretics such as vasopressin receptor antagonists may have a role in treatment as well. Well-designed clinical trials are essential to guide therapy of refractory oedema in NS. In this review, the authors discuss the pathogenesis of oedema formation in patients with NS and propose a treatment algorithm for management of resistant oedema based on the limited available evidence.

Periplocymarin Plays an Efficacious Cardiotonic Role via Promoting Calcium Influx.

Periplocymarin, which belongs to cardiac glycosides, is an effective component extracted from Periplocae Cortex. However, its cardiovascular effects remain unidentified. In the present study, injection of periplocymarin (5 mg/kg) through external jugular vein immediately increased the mean arterial pressure (MAP) in anesthetized C57BL/6 mice. Ex vivo experiments using mouse mesenteric artery rings were conducted to validate the role of periplocymarin on blood vessels. However, periplocymarin failed to induce vasoconstriction directly, and had no effects on vasoconstriction induced by phenylephrine (Phe) and angiotensin II (Ang II). In addition, vasodilatation induced by acetylcholine (Ach) was insusceptible to periplocymarin. Echocardiography was used to evaluate the effects of periplocymarin on cardiac function. The results showed that the injection of periplocymarin significantly increase the ejection fraction (EF) in mice without changing the heart rate. In vitro studies using isolated neonatal rat ventricular myocytes (NRVMs) revealed that periplocymarin transiently increased the intracellular Ca2+ concentration observed by confocal microscope. But in Ca2+-free buffer, this phenomenon vanished. Besides, inhibition of sodium potassium-activated adenosine triphosphatase (Na+-K+-ATPase) by digoxin significantly suppressed the increase of MAP and EF in mice, and the influx of Ca2+ in cardiomyocytes, mediated by periplocymarin. Collectively, these findings demonstrated that periplocymarin increased the contractility of myocardium by promoting the Ca2+ influx of cardiomyocytes via targeting on Na+-K+-ATPase, which indirectly led to the instantaneous rise of blood pressure.

Mitochondria are main targets of time/dose-dependent oxidative damage-based hepatotoxicity caused by rhizoma dioscoreae bulbiferae in mice

Background: Rhizoma Dioscoreae bulbiferae could cause liver damage, which limited its application in the clinic. Aims and Objectives: To explore the mechanism of hepatotoxicity of Rhizoma Dioscoreae bulbiferae in mice. Materials and Methods: In the present study, the water extraction of Rhizoma Dioscoreae bulbiferae (W.E.R) was administrated via intragastrical with Low (19.6 g/kg), Middle (28.0 g/kg), and High (40.0 g/kg) dose in mice. At each time point 14 days, 21 days, and 28 days, the body weight, liver coefficient, indexes of liver function alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate transaminase (AST), various biochemical biomarkers of liver tissue and mitochondria were detected and analyzed. Results: We found that W.E.R could decrease the body weight, increase the liver coefficient and the expression levels of indexes of liver function in mice. Next, we investigated that W.E.R could increase the expression levels of reactive oxygen species (ROS) and malondialdehyde (MDA), decrease the expression levels of adenosine triphosphate (ATP) and improve the enzyme activities of total superoxide dismutase (SOD). Third, we found that W. E. R could increase the enzyme activities of manganese-superoxide dismutase, decrease the enzyme activities of sodium-potassium adenosine triphosphatase (Na + -K + -ATPase) and calcium-magnesium adenosine triphosphatase (Ca 2+ -Mg 2+ -ATPase). Finally, we analyzed that there were significant negative correlations between body weight, expression level of ATP, activity of Na + -K + -ATPase, activity of Ca 2+ -Mg 2+ -ATPase and time, dose. There were significant positive correlations between liver coefficient, ALP, ALT, AST, expression levels of ROS, MDA and time, dose. Conclusion: All the results above indicated that W.E.R could cause the hepatotoxicity based on the oxidative damage in mice, which and mitochondria might be the main targets.

Effects of dietary n-3HUFA on juvenile white shrimp, Litopenaeus vannamei: Growth, feed utilization, antioxidant enzymes activities and fatty acid compositions

Present study investigates the effects of n-3 high-unsaturated fatty acid (n-3HUFA) levels on growth performance, antioxidant enzymes activities and fatty acid compositions of juvenile Litopenaeus vannamei. These represented seven iso-nitrogenous and iso-lipidic diets. Analysed n-3HUFA concentrations were 0.16% (control), 0.48%, 0.74%, 1.39%, 2.39%, 2.92% and 3.44% respectively. A total of 840 juvenile L. vannamei were randomly stocked into 21 0.5 m3 tanks for 56 days. A significant increase (p < 0.05) was observed from 0.16% to 0.74% n-3HUFA and a decrease when n-3HUFA was above these levels in weight gain rate (WGR) and specific growth rate. Total cholesterol, triglyceride and low-density lipoprotein in serum showed a significant decrease, high-density lipoprotein showed a significant increase (p < 0.05). Phenoloxidase activity in serum and sodium-potassium adenosine triphosphatase activity in gill were significantly affected by dietary n-3HUFA (p < 0.05), both of them showing a downward trend after upward. Malic dehydrogenase and superoxide dismutase activities in serum were also significantly affected by dietary n-3HUFA (p < 0.05), which rose first and then decreased in general, both of them have a maximum in 2.39% group. No significant differences of the activities of aspartate transaminase and alanine transaminase were observed among all groups (p > 0.05). With dietary n-3HUFA increase, both ∑HUFA and n-3HUFA contents gradually increased in hepatopancreas and tail muscles (p < 0.05). Based on broken-line regression analysis of WGR, the optimal n-3HUFA requirement is 0.89% for juvenile L. vannamei with initial weight of 0.50 ± 0.01 g.

Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of Na+,K+-ATPase in pancreatic acinar cells.

Rat pancreatic acinar cells possess only the p21-activated kinase (PAKs), PAK4 of the group II PAK, and it is activated by gastrointestinal hormones/neurotransmitters stimulating PLC and by a number of growth factors. However, little is known generally of cAMP agents causing PAK4 activation, and there are no studies with gastrointestinal hormones/neurotransmitters activating cAMP cascades. In the present study, we examined the ability of VIP and secretin, which stimulate cAMP generation in pancreatic acini, to stimulate PAK4 activation, the signaling cascades involved, and their possible role in activating sodium-potassium adenosine triphosphatase (Na+,K+-ATPase). PAK4 activation was compared with activation of the well-established cAMP target, cyclic AMP response element binding protein (CREB). Secretin-stimulated PAK4 activation was inhibited by KT-5720 and PKA Type II inhibitor (PKI), protein kinase A (PKA) inhibitors, whereas VIP activation was inhibited by ESI-09 and HJC0197, exchange protein directly activated by cAMP (EPAC) inhibitors. In contrast, both VIP/secretin-stimulated phosphorylation of CREB (pCREB) via EPAC activation; however, it was inhibited by the p44/42 inhibitor PD98059 and the p38 inhibitor SB202190. The specific EPAC agonist 8-CPT-2- O-Me-cAMP as well 8-Br-cAMP and forskolin stimulated PAK4 activation. Secretin/VIP activation of Na+,K+-ATPase, was inhibited by PAK4 inhibitors (PF-3758309, LCH-7749944). These results demonstrate PAK4 is activated in pancreatic acini by stimulation of both VIP-/secretin-preferring receptors, as is CREB. However, they differ in their signaling cascades. Furthermore, PAK4 activation is needed for Na+,K+ATPase activation, which mediates pancreatic fluid secretion. These results, coupled with recent studies reporting PAKs are involved in both pancreatitis/pancreatic cancer growth/enzyme secretion, show that PAK4, similar to PAK2, likely plays an important role in both pancreatic physiological/pathological responses. NEW & NOTEWORTHY Pancreatic acini possess only the group II p21-activated kinase, PAK4, which is activated by PLC-stimulating agents/growth factors and is important in enzyme-secretion/growth/pancreatitis. Little information exists on cAMP-activating agents stimulating group II PAKs. We studied ability/effect of cyclic AMP-stimulating agents [vasoactive intestinal polypeptide (VIP), secretin] on PAK4 activity in rat pancreatic-acini. Both VIP/secretin activated PAK4/CREB, but the cAMP signaling cascades differed for EPAC, MAPK, and PKA pathways. Both hormones require PAK4 activation to stimulate sodium-potassium adenosine triphosphatase activity. This study shows PAK4 plays an important role in VIP-/secretin-stimulated pancreatic fluid secretion and suggests it plays important roles in pancreatic acinar physiological/pathophysiological responses mediated by cAMP-activating agents.

Effects of acetone extract of Cola nitida on brain sodium-potassium adenosine triphosphatase activity and spatial memory in healthy and streptozotocin-induced diabetic female Wistar rats.

Background This study was carried out to investigate the effects of acetone extract of Cola nitida on brain Na+/K+-ATPase activity and spatial memory of healthy and streptozotocin (STZ)-induced diabetic female Wistar rats. Methods Forty-two female Wistar rats were used for this study and were randomly distributed into six groups (n=7). Rats in group 1 were used as control and were administered normal saline; group 2 rats were healthy rats administered 50 mg/kg of kola nut extract per day; group 3 rats were healthy rats administered 100 mg/kg of kola nut extract per day; group 4 rats were a diabetic group also administered normal saline; group 5 rats were diabetic rats administered 50 mg/kg of kola nut extract per day; and group 6 rats were diabetic rats administered 100 mg/kg of kola nut extract per day. Diabetes was induced with 50 mg/kg of STZ. After 3 weeks of administration, the spatial memories of the rats were tested using the Y-maze, followed by assay of Na+/K+-ATPase activity. Results The result shows a significant increase in Na+/K+-ATPase activity of diabetic treated groups (5 and 6) when compared with the diabetic group (4) and a significant increase in Na+/K+-ATPase activity of healthy treated groups (2 and 3) when compared with control. Also, there was a significant increase in spatial memory of the diabetic treated groups when compared with diabetic group. Conclusions This study revealed that kola nut extract has restorative effect on brain Na+/K+-ATPase activities and spatial memory of STZ-induced diabetic female Wistar rats.

Histopathological findings of renal tissue induced by oxidative stress due to different concentrations of fluoride.

It has been reported that excessive intake of fluoride can induce renal lesions. However, its pathogenesis is still less understood. Therefore, this study was conducted to investigate oxidative damage and the relationships between the oxidative damage and renal lesions in fluoride-treated mice by using the methods of histopathology, biochemistry, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). A total of 240 ICR mice were randomly divided into four equal groups (sodium fluoride was given orally at the dose of 0, 12, 24 and 48 mg/kg body weight for 42 days, respectively). We found that fluoride in excess of 12 mg/kg induced renal oxidative damage, which was characterized by increasing the levels of reactive oxygen species (ROS) production and contents of malondialdehyde (MDA) and protein carbonyls (PC), and decreasing the abilities of anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR), glutathione (GSH) content, as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px). Concurrently, fluoride caused degeneration and necrosis of the tubular cells, renal tubular hyaline casts and glomeruli swelling, which were consistent with the alteration of renal function parameters including elevated contents of serum creatinine (Cr), serum uric acid (UA), blood urea nitrogen (BUN), and the activities of urinary N-acetyl-b-D-glucosaminidase (NAG), renal lactate dehydrogenase (LDH), and reduced activities of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and acid phosphatase (ACP) in the kidney. The above-mentioned results showed that fluoride in excess of 12 mg/kg induced renal oxidative damage, which then caused renal lesions and dysfunctions. These findings also clearly demonstrated that oxidative damage is one of the mechanisms of fluoride-induced renal lesions and dysfunctions.

Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-κB pathway and reduction of anti-inflammatory mediator expression in the kidney

Nickel (Ni) or Ni compounds target a number of organs and produce multiple toxic effects. Kidney is the major organ for Ni accumulation and excretion. There are no investigations on the Ni- or Ni compounds-induced renal inflammatory responses in human beings and animals at present. Therefore, we determined NiCl2-caused alteration of inflammatory mediators, and functional damage in the broiler's kidney by the methods of biochemistry, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Dietary NiCl2 in excess of 300 mg/kg caused the renal inflammatory responses that characterized by increasing mRNA expression levels of the pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) via the activation of nucleic factor κB (NF-κB), and decreasing mRNA expression levels of the anti-inflammatory mediators including interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-13 (IL-13). Concurrently, NiCl2 caused degeneration, necrosis and apoptosis of the tubular cells, which was consistent with the alteration of renal function parameters including elevated alkaline phosphatase (AKP) activity, and reduced activities of sodium-potassium adenosine triphosphatase (Na(+)/K(+)-ATPase), calcium adenosine triphosphatase (Ca(2+)-ATPase), lactic dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) in the kidney. The above-mentioned results present that the activation of NF-κB pathway and reduction of anti-inflammatory mediator expression are main mechanisms of NiCl2-caused renal inflammatory responses and that the renal function is decreased or impaired after NiCl2-treated.

Neuroprotective Effect of Punicalagin against Cerebral Ischemia Reperfusion-induced Oxidative Brain Injury in Rats

Punicalagin (PG) is a hydrolyzable polyphenol in Punica granatum. It has been previously reported that it has a protective effect against hypoxia-induced ischemia brain injury. It is a potent antioxidant. The present study is aimed to evaluate the antioxidant potential of PG against focal cerebral ischemia-reperfusion injury in rats subjected to middle cerebral artery occlusion (MCAO). Rats were randomly divided into sham, MCAO, PG-treated groups. PG (15 and 30 mg/kg) vehicle was administered orally for 7 days before MCAO. Rats were anesthetized with ketamine (100 mg/kg), xylazine (10 mg/kg), and subjected to 2 hours occlusion, and 22 hours reperfusion. Neurologic deficit, brain water content (BWC), histopathology changes, and oxidative stress markers were evaluated after 22 hours of reperfusion. In comparison with MCAO model group, treatment with PG significantly reduced the neurologic deficit scores and BWC. PG-attenuated neuronal damage occurred by downregulating the levels of malondialdehyde, sodium-potassium adenosine triphosphatase activity, nitric oxide, protein carbonyl content, and mitochondria-generated reactive oxygen species and upregulating the superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, glutathione reductase activities. Taken together, these results suggested that supplementation of PG treatment effectively ameliorates the cerebral ischemia/reperfusion induced oxidative damage by virtue of its antioxidant potential.

Aqueous exposure to 4‐nonylphenol and 17β‐estradiol increases stress sensitivity and disrupts ion regulatory ability of juvenile Atlantic salmon

Population declines of wild Atlantic salmon have been attributed to an array of anthropogenic disturbances, including dams, commercial and recreational fishing, habitat loss, and pollution. Environmental contaminants in particular, can act as environmental stressors on fish, typically causing disruption of ion homeostasis due to their close association with the aquatic environment. To examine the effects of the xenoestrogen 4-nonylphenol (NP) or 17beta-estradiol (E2) on stress sensitivity and ion regulation, we exposed juvenile Atlantic salmon continuously for 21 d to either 10 or 100 microg/L NP (NP-L or NP-H), 2 microg/L E2 (positive control), or vehicle control during the parr-smolt transformation in April. After treatment, fish were sampled in freshwater (FW), transferred to 30 per thousand seawater (SW) for 24 h, or subjected to a handling stress. Estradiol and NP-H increased plasma vitellogenin in males and females, and E2 increased gonadosomatic index only in males. In FW, E2 reduced sodium potassium-activated adenosine triphosphatase activity as well as plasma levels of growth hormone, insulin-like growth factor I, and triiodothyronine. Both E2 and NP-H reduced plasma sodium in FW and increased plasma chloride in SW. Plasma cortisol levels pre- and poststressor were significantly elevated by all treatments relative to controls, but only E2 increased plasma glucose before and after the stressor. These results indicate that exposure of anadromous salmonids to environmental estrogens heightens sensitivity to external stressors, impairs ion regulation in both FW and SW, and disrupts endocrine pathways critical for smolt development.

Neurotoxicity Evaluation of the Organofluorine Pesticide Etoxazole in the Brain of Oreochromis niloticus

Etoxazole is a new organofluorine pesticide that has been used worldwide as acaricide and insecticide since 1998. Almost no previous attempt has been made to evaluate the toxic effects of etoxazole in vertebrates. Using fish (Oreochromis niloticus) as a suitable model organism, the aim of this study was to indicate whether etoxazole affects acetylcholinesterase and sodium potassium–activated adenosine triphosphatase activities in the brain tissue in order to evaluate the impacts on neurotoxicity and ion transportation. Enzyme activities were determined using spectrophotometric methods. At the sublethal concentrations (0.27, 0.54, 0.81, 1.08, 1.35 mg/L) and exposure durations (1, 7, 15 days) tested, etoxazole has no inhibitory effect on the brain acetylcholinesterase and sodium potassium–activated adenosine triphosphatase activities. Our results suggest that etoxazole and/or its metabolites may not reach or penetrate the blood–brain barrier; therefore, they do not essentially alter the functions of these two important enzymes for the brain.

Low-salinity tolerance of juvenile fugu Takifugu rubripes

To study the adaptability of juvenile fugu Takifugu rubripes to low-salinity environments, fish were transferred from full-strength seawater (100% SW) to freshwater (FW) and 25, 50, 75 and 100% SW, and checked for mortality over 3 days. No mortality was observed in 25–100% SW, whereas all fish died in FW. In fish transferred to 25–100% SW, blood osmolality was maintained within a physiological range. To further explore the lower limit of salinity that fugu could tolerate, fish were transferred from 100% SW to FW and 1, 5, 10, 15 and 25% SW. All fish survived in 5–25% SW, but fish died in FW and 1% SW. In fish surviving transfer to FW and 1 and 5% SW, blood osmolality was decreased to a near sublethal level of approximately 300 mOsm/kg·H2O. Therefore, the lower limit of salinity tolerance is estimated to lie between 5 and 10% SW. Preacclimation in 25% SW for 7 days did not essentially affect the survival salinity range. Although survival rates and blood osmolality were slightly improved by preacclimation in 25% SW, blood osmolality was markedly decreased in salinities less than 10% SW, as was seen in the direct transfer. Neither chloride cell morphology nor sodiumpotassium adenosinetriphosphatase activity in the gills showed a significant change following transfer to low salinities. These findings indicate that fugu can be adapted to hypoosmotic environments to some extent, exerting hyperosmoregulatory ability, although chloride cells are less likely to absorb ions in hypoosmotic environments.

Sodium potassium adenosine triphosphatase activity in preterm and term infants and its possible role in sodium homeostasis during maturation

AIMTo investigate sodium (NA+) potassium (K+) adenosine triphosphatase (ATPase) activity in newborn infants at different gestational ages, to elucidate the mechanism underlying poor renal sodium conservation in preterm infants.METHODSFifty three...

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, stimulates nitric oxide production and sodium potassium adenosine triphosphatase activity in SH-SY5Y human neuroblastoma cells

Deficiencies in cellular cyclic AMP (cAMP) and nitric oxide (NO) production are thought to be involved in the pathogenesis of diabetic neuropathy. We used a human neuroblastoma cell line, SH-SY5Y, to investigate the effect of cilostazol, a specific cAMP phosphodiesterase inhibitor, on NO production and Na +, K +-ATPase activity. SH-SY5Y cells were cultured under 5 or 50 mM glucose for 5–6 days, the cells were then exposed to cilostazol or other chemicals and nitrite, cAMP and Na +, K +-ATPase activity were measured. In cells grown in 50 mM glucose, cilostazol was observed to increase significantly both NO production and cellular cAMP accumulation in a time- and dose-dependent manner. Cilostazol also significantly recovered reduced levels of protein kinase A activity (PKA) in 50 mM glucose. Furthermore, a PKA inhibitor, H-89 significantly suppressed the increase in NO production stimulated by cilostazol, suggesting that cilostazol stimulates NO production by activating PKA. Cilostazol did not affect either sorbitol or myo-inositol concentrations. Dexamethazone, which is known to induce inducible NO synthase, had no effect on NO production stimulated by cilostazol, suggesting that cilostazol stimulates NO production catalyzed by neuronal constitutive NO synthase (ncNOS) in SH-SY5Y cells. L-arginine, which is an NO agonist enhanced Na +, K +-ATPase activity in cells grown in 50 mM glucose, NG-nitro-L-arginine methyl ester (L-NAME), which is an NOS inhibitor inhibited basal Na +, K +-ATPase activity in 5 mM glucose and suppressed the increased enzyme activity induced by cilostazol in 50 mM glucose. The above results confirmed our previous observation that NO regulates Na +, K +-ATPase activity in SH-SY5Y cells and suggest that cilostazol increases Na +, K +-ATPase activity, at least in part, by stimulating NO production. The present results also suggest that cilostazol has a beneficial effect on diabetic neuropathy by improving Na +, K +-ATPase activity via directly increasing cAMP and NO production in nerves.

Role of Na(+)-K(+)-ATPase activity in regulation of detrusor contractility and diabetic bladder dysfunction.

Sodium-potassium activated adenosine triphosphatase (Na+-K+-ATPase) is a ubiquitously expressed enzyme which utilizes the energy derived from ATP hydrolysis to transport Na+ and K+ across the plasma membrane. Na+-K+-ATPase is composed of a catalytic a (~110 kDa) subunit, and a glycosylated β subunit (35 kDa) which is required for the enzyme activity.1 Three isoforms of the a-subunit (a1, a2, a3) and two isoforms of β subunit (β1 and β2), encoded by a highly conserved multigene family, have been reported.1 The expression of these genes has been shown to be hormonally regulated, and tissue and species specific.1 Our recent studies using specific monoclonal antibodies indicate that bladder smooth muscle expresses all the a and b1 isoforms of Na+-K+-ATPase (unpublished data).

Continuous warm versus intermittent cold cardioplegic infusion: A comparison of energy metabolism, sodium-potassium adenosine triphosphatase activity, and postischemic functional recovery in the blood-perfused rat heart

We used metabolic, enzymatic, and functional end points to compare the protective properties of continuous warm and intermittent cold cardioplegic infusion in isolated, blood-perfused rat hearts. After excision, hearts ( n = 12 per group) were preserved for 3 hours by one of the following cardioplegic procedures: (1) continuous infusion of warm (37º C) blood cardioplegic solution prepared by mixing Fremes' solution with rat arterial blood in a ratio of 1:4, (2) continuous infusion of warm (37º C) crystalloid cardioplegic solution prepared by mixing Fremes' solution with bicarbonate buffer solution in a ratio of 1:4, or (3) intermittent infusion of cold (20º C) St. Thomas' Hospital cardioplegic solution number 2 infused for 3 minutes every 30 minutes during a 3-hour period of ischemia. In the continuous-infusion cardioplegic groups, the solution was infused through the aorta at a flow rate of 0.8 ml · min -1 · gm -1 heart. At the end of the 3-hour preservation period, myocardial sodium-potassium adenosine triphosphatase activity (an index of ion-exchange activity) was assessed in six hearts in each group. The remaining hearts in each group were then aerobically perfused at 37º C with arterial blood (from a support rat) for a further 50 minutes, during which time they were atrially paced at 320 beats/min. At the end of this period, left ventricular developed and end-diastolic pressures were assessed with an intraventricular balloon; the hearts were then freeze-clamped and taken for the measurement of tissue adenosine triphosphate and creatine phosphate content. Hearts ( n = 6) aerobically perfused with blood for 50 minutes (no cardioplegic infusion) served as control preparations. At a balloon volume of 180 μl, the mean final values for left ventricular developed pressure in the continuous warm blood, continuous warm crystalloid, and intermittent cold cardioplegic groups were 98 ± 5 mm Hg ( p < 0.05), 70 ± 5 mm Hg, and 78 ± 5 mm Hg, respectively. This was compared with 122 ± 5 mm Hg in control hearts ( p < 0.05 vs the rest). For left ventricular end-diastolic pressure, the corresponding values were 33 ± 3 mm Hg, 32 ± 6 mm Hg, and 14 ± 4 mm Hg ( p < 0.05), respectively. The control value was 16 ± 3 mm Hg ( p < 0.05 vs continuous warm blood and continuous warm crystalloid groups). Tissue content of adenosine triphosphate was similarly reduced to approximately 50% of control values in all groups, and creatine phosphate content fully recovered in all groups. Sodium-potassium adenosine triphosphatase activity was poorly preserved in continuous warm crystalloid–treated hearts (0.012 ± 0.003 vs 0.030 ± 0.008 μmol inorganic phosphate · mg -1 · min -1 in control preparations, p < 0.05), whereas in continuous warm blood and intermittent cold cardioplegic groups (0.032 ± 0.015 and 0.031 ± 0.013 μmol inorganic phosphate · mg -1 · min -1) there was no significant loss of activity. In conclusion, (1) none of the procedures conferred complete protection, (2) continuous warm blood cardioplegic infusion provided superior preservation of systolic function and intermittent cold cardioplegic infusion afforded superior protection with respect to diastolic function, and (3) both continuous warm blood and intermittent cold cardioplegic infusion similarly protected sodium-potassium adenosine triphosphatase activity and tissue adenosine triphosphate and creatine phosphate content, whereas continuous warm crystalloid cardioplegic infusion afforded poor preservation of sodium-potassium adenosine triphosphatase activity. In general, the poorest protection was afforded by continuous warm crystalloid cardioplegic infusion. (J T HORAC C ARDIOVASC S URG 1996;112:797-805)

The possible role of sodium-potassium adenosine triphosphatase in preterm labour

An unacceptably high incidence of preterm labour is seen in the black and coloured communities of South Africa. This hypothesis proposes that sodium-potassium adenosine triphosphatase activity plays an important role in preterm labour. The impaired activity of the sodium pump leads to increased cytosolic calcium levels, which may trigger contraction of myometrial smooth-muscle cells, resulting in preterm labour.

Effects of Lead and a Low-Molecular-Weight Endogenous Plasma Inhibitor on the Kinetics of Sodium—Potassium-Activated Adenosine Triphosphatase and Potassium-Activated p-Nitrophenylphosphatase

1. Lead, ouabain and an endogenous plasma inhibitor were all found to be potent inhibitors of purified hog cerebral cortex sodium-potassium-activated adenosine triphosphatase and potassium-stimulated p-nitrophenyl-phosphatase. 2. The kinetic characteristics of inhibition of both enzymes by lead and the endogenous plasma inhibitor differed in several respects. For sodium-potassium-activated adenosine triphosphatase, lead and the endogenous plasma inhibitor were non-competitive inhibitors with respect to potassium; lead was competitive with respect to sodium, whereas the endogenous plasma inhibitor had no effect; lead was competitive with respect to magnesium adenosine triphosphate, whereas the endogenous plasma inhibitor was uncompetitive. For potassium-activated p-nitrophenylphosphatase, both lead and the endogenous plasma inhibitor were competitive with respect to potassium; lead showed a mixed type of inhibition with respect to p-nitrophenylphosphate, whereas the endogenous plasma inhibitor was non-competitive. 3. Lead and the endogenous plasma inhibitor exhibited synergistic inhibitory activity on sodium-potassium-activated adenosine triphosphatase. 4. These results suggest that lead could play a contributory role in the pathogenesis of essential hypertension via an additive inhibition of vascular smooth muscle sodium-potassium-activated adenosine triphosphatase.

Abnormalities of sodium transport by sodium, potassium-activated adenosine triphosphatase in erythrocytes from obese children.

1. Intracellular Na+ concentration [Na+]i and Na+ extrusion catalysed by sodium potassium-activated adenosine triphosphatase (Na+, K+-pump) were evaluated in erythrocytes from 21 obese children and 20 normal weight- and age-matched controls. 2. Obese children showed a significantly decreased Vmax. for Na+, K+-pump-mediated Na+ efflux (5638 +/- 338 vs 7597 +/- 335 mumol h-1 litre-1 of cells mean +/- SEM, P = 0.01), while [Na+]i (9.3 +/- 0.3 vs 9.1 +/- 0.5 mmol/litre of cells, mean +/- SEM, NS) and Na+ efflux in fresh cells (2380 +/- 153 vs 2533 +/- 180 mumol h-1 litre-1 of cells, mean +/- SEM, NS) were similar in both groups. 3. Mean diastolic blood pressure was significantly higher in obese children than in controls, although both groups were normotensive (73.8 +/- 1.3 vs 66.2 +/- 1.9 mmHg, mean +/- SEM, P = 0.009). 4. Abnormal Na+, K+-pump activity is present in individuals with idiopathic obesity. 5. The possible link between obesity and blood pressure regulation may be mediated through modifications in Na+,K+-pump activity.

Cardiovascular and sympathetic responses to ouabain injected into the hypothalamus in rats.

To investigate the effects of sodium-potassium activated adenosine triphosphatase inhibition on central cardiovascular regulation a microinjection of ouabain was given into the hypothalamus of urethane anaesthetised rats. Doses of 0.01-1.0 micrograms per rat injected into the posterior hypothalamus produced a rise in blood pressure within 1 min, the maximum rise occurring 15-20 min later in a dose dependent manner. Both heart rate and abdominal sympathetic nerve activity increased with the rise in blood pressure. Ouabain injected into either the anterior preoptic hypothalamus or the ventromedial hypothalamus produced no notable cardiovascular responses. These results suggest that an endogenous digitalis like substance produced in the hypothalamus as a result of sodium loading may participate in central cardiovascular regulation by increasing sympathetic outflow in the discrete area of the brain, as does ouabain.