Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl^-]_i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl^-]_i. High [Cl^-]_i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.
Blood Pressure ; Diet ; Humans ; Kidney/metabolism* ; Kidney Tubules, Distal/metabolism* ; Phosphorylation ; Potassium/pharmacology* ; Protein Serine-Threonine Kinases ; Solute Carrier Family 12, Member 3/metabolism*

BACKGROUND: Information on biochemical changes following rapid transfusion of blood mixtures in liver transplantation patients is limited. METHODS: A blood mixture composed of red blood cells, fresh frozen plasma, and 0.9% saline was prepared in a ratio of 1 unit:1 unit:250 ml. During massive hemorrhage, 300 ml of the blood mixture was repeatedly transfused. A blood mixture sample as well as pre- and post-transfusion arterial blood samples were collected at the first, third, fifth, and seventh bolus transfusions. Changes in pH, hematocrit, electrolytes, and glucose were measured with a point-of-care analyzer. The biochemical changes were described, and the factors driving the changes were sought through linear mixed effects analysis. RESULTS: A total of 120 blood samples from 10 recipients were examined. Potassium and sodium levels became normalized during preservation. Biochemical changes in the blood mixture were significantly related to the duration of blood bank storage and reservoir preservation (average R2 = 0.41). Acute acidosis and hypocalcemia requiring immediate correction occurred with each transfusion. Both the pre-transfusion value of the patient and the blood mixture value were significant predictors of post-transfusion changes in the body (average R2 = 0.87); however, the former was more crucial. CONCLUSIONS: Rapid infusion of blood mixture is relatively safe because favorable biochemical changes occur during storage in the reservoir, and the composition of the blood mixture has little effect on the body during rapid transfusion in liver recipients. However, acute hypocalcemia and acidosis requiring immediate correction occurred frequently due to limited citrate metabolism in the liver recipients.
Acidosis ; Blood Banks ; Blood Safety ; Blood Transfusion ; Citric Acid ; Electrolytes ; Erythrocytes ; Glucose ; Hematocrit ; Hemorrhage ; Humans ; Hydrogen-Ion Concentration ; Hypocalcemia ; Liver Transplantation* ; Liver* ; Metabolism ; Plasma ; Point-of-Care Systems ; Potassium ; Sodium

OBJECTIVETo investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

METHODSThe ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

RESULTSPreconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca sensitive-K channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

CONCLUSIONBAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca sensitive-K (BK and IK) channels in the corpus cavernosum.

Animals ; Area Under Curve ; Berberis ; chemistry ; Blood Pressure ; drug effects ; Cyclic GMP ; metabolism ; Epoprostenol ; pharmacology ; In Vitro Techniques ; Indomethacin ; pharmacology ; Male ; Models, Biological ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Penile Erection ; drug effects ; Phenylephrine ; pharmacology ; Plant Extracts ; pharmacology ; Potassium Channel Blockers ; pharmacology ; Potassium Channels ; metabolism ; Pressure ; Rabbits

BACKGROUND/AIMS: To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. METHODS: Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. RESULTS: A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia (< 3.5 mmol/L) was the most common type of electrolyte disturbance observed at 21.9%. A decrease in serum potassium levels was associated with decreases in blood glucose levels (r = 0.151, p = 0.025). During severe hypoglycemia, median blood glucose levels, incidence of tachycardia (> 100 beats per minute) and severe hypertension (> or = 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. CONCLUSIONS: During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.
Aged ; Aged, 80 and over ; Biomarkers/blood ; Blood Glucose/drug effects/*metabolism ; Diabetes Mellitus, Type 2/blood/diagnosis/drug therapy/*epidemiology ; Emergency Service, Hospital ; Female ; Humans ; Hypertension/chemically induced/epidemiology ; Hypoglycemia/blood/chemically induced/diagnosis/*epidemiology/therapy ; Hypoglycemic Agents/adverse effects ; Hypokalemia/blood/chemically induced/diagnosis/*epidemiology ; Male ; Middle Aged ; Potassium/*blood ; Republic of Korea/epidemiology ; Risk Factors ; Severity of Illness Index ; Tachycardia/chemically induced/epidemiology ; *Water-Electrolyte Balance/drug effects

Abnormal cholesterol metabolism is associated with an elevated risk of developing atherosclerosis, hypertension, and diabetes etc. Na(+)/K(+)-ATPase was found to regulate cholesterol synthesis, distribution and trafficking. This study aimed to examine the effect of high-fat diet on cholesterol metabolism in rats and the role of Na(+)/K(+)-ATPase/Src/ERK signaling pathway in the process. Forty male SD rats were evenly divided into high-fat diet group and control group at random. Animals in the former group were fed on high-fat diet for 12 weeks, and those fed on basic diet served as control. Blood lipids, including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesteral (LDL-C) levels, were detected at 3, 6 and 12 weeks. The ratio of cholesterol content in cytoplasm to that in cell membrane was detected in liver tissues. RT-PCR and Western blotting were used to measure the expression of lipid metabolism-associated genes (HMG-CoA reductase and SREBP-2) after 12-week high-fat diet. Na(+)/K(+)-ATPase/Src/ERK signaling pathway-related components (Na(+)/K(+)-ATPase α1, Src-PY418 and pERK1/2) were also measured by Western blotting. The results showed that the serum TC, TG, and LDL-C levels were significantly higher in high-fat diet group than those in control group, while the HDL-C level was significantly lower in high-fat diet group at 6 weeks (P<0.01). High-fat diet led to an increase in the cholesterol content in the cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to that in cell membrane was elevated over time. The expression of HMG-CoA reductase and SREBP-2 was significantly suppressed at mRNA and protein levels after 12-week high-fat diet (P<0.05). Moreover, high-fat diet promoted the expression of Na(+)/K(+)-ATPase α1 but suppressed the phosphorylation of Src-PY418 and ERK1/2 at 12 weeks (P<0.05). It was concluded that high-fat diet regulates cholesterol metabolism, and Na(+)/K(+)-ATPase signaling pathway is involved in the process possibly by regulating the expression of lipid metabolism-associated proteins HMG-CoA reductase and SREBP-2.
Acyl Coenzyme A ; genetics ; metabolism ; Animals ; Cell Membrane ; metabolism ; Cholesterol ; blood ; Cytoplasm ; metabolism ; Diet, High-Fat ; adverse effects ; Gene Expression Regulation ; drug effects ; Lipid Metabolism ; drug effects ; Liver ; metabolism ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; genetics ; metabolism ; Sterol Regulatory Element Binding Protein 2 ; genetics ; metabolism

OBJECTIVETo investigate the changes in lung injury and oxidative stress of sprague-Dawleyy (SD) rats at different times after single intratracheal instillation of potassium dichromate.

METHODSA total of 50 healthy male SD rats were randomly divided into control group and potassium dichromate group. The potassium dichromate group and the control group received 3 ml/kg intratracheal instillation of K2Cr2O7 (1.5 mg/kg) and normal saline, respectively. Rats in these two groups were sacrificed in batches at 1, 3, 7, 14, and 28 days after exposure. The changes in the following indices were observed and analyzed: body weight, lung coefficient, alkaline phosphatase (AKP) in bronchoalveolar lavage fluid, glutathione peroxidase (GSH-Px) in lung homogenate, and reduced glutathione (GSH) in serum.

RESULTSThe rats in the potassium dichromate group had significantly decreased body weight on day 1 and day 3 after exposure than the control group (P<0.05). Lung coefficient increased significantly on day 7 (P<0.05) and kept increasing until the end of the experiment. The potassium dichromate group had a significantly higher activity of AKP than the control group on day 1 and day 7 after exposure (P<0.05). However, the potassium dichromate group had a significantly lower activity of GSH-Px than the control group on day 1 and day 3 after exposure (P<0.05). And the potassium dichromate group had a lower activity of reduced GSH than the control group on day 3 and day 7 after exposure.

CONCLUSIONSingle intratracheal instillation of 1.5 mg/kg potassium dichromate could result in lung inflammatory injury. of SD rats, and the injury is more severe on day 7 after exposure. Body injury is related to antioxidant activity, and the antioxidant.activity cannot recover completely on day 28 after exposure.

Alkaline Phosphatase ; metabolism ; Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Glutathione ; blood ; Glutathione Peroxidase ; metabolism ; Lung ; physiopathology ; Lung Injury ; chemically induced ; physiopathology ; Male ; Oxidative Stress ; Potassium Dichromate ; toxicity ; Rats ; Rats, Sprague-Dawley

The purposes of this study were to investigate the effect of emodin on expression of BKCa channel β1 subunit in basilar artery smooth muscle cells (BASMCs) and electrophysiological characteristics of vascular smooth muscle cells in spontaneously hypertensive rats (SHR). Tail artery pressure measurement instrument was used to measure the change of SHR systolic blood pressure before and after emodin intervention. Single vascular smooth muscle cell was electrically recorded by whole-cell patch-clamp technique. Immunohistochemistry and Western blotting were used to study the distribution and expression of the BKCa channel β1 subunit. The results showed that emodin decreased blood pressure of SHR from (223 ± 16) mmHg to (127 ± 12) mmHg (P < 0.01). There was no difference of blood pressure between emodin-treated SHR and Wistar rats. Emodin significantly increased outward currents of smooth muscle cells in SHR (P < 0.05), and this effect could be reversed by specific inhibitor of BKCa channel, IbTX. Emodin also up-regulated BKCa channel β1 subunit expression in BASMCs. These results suggest that emodin relaxes cerebral basilar artery by enhancing BKCa current via increasing β1 subunit expression in BASMCs.
Animals ; Basilar Artery ; cytology ; Blood Pressure ; Emodin ; pharmacology ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits ; metabolism ; Myocytes, Smooth Muscle ; metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Vasodilation ; Vasodilator Agents ; pharmacology

BACKGROUNDOuabain and digoxin are important cardiac glycoside and related to many cardiovascular diseases. The purpose of this study was to investigate the changes of sodium pump α-subunit expression in rats and compare the effects of ouabain (OUA) and digoxin (DIG) on the development of hypertension.

METHODSIn situ hybridization was performed. Specific sequence oligonucleotide probe tailing with a Dig-dUTP hybrid to target nucleic acids of the sodium pump α-subunit. According to counting positive particles sodium pump subunit expression was analyzed with statistical methods.

RESULTSOn day 16 of drug administration, the blood pressure of rats increased significantly in the OUA group. In the DIG group, the blood pressure revealed no significant difference when compared to the control group. In addition, the effects of OUA and DIG on sodium pump α-subunit RNA expression in tissues differed.

CONCLUSIONSOUA and DIG can not only change the configuration of the sodium pump to depress their activity, but also influence their gene expression which is important in the mechanism of hypertension. This may be a key point in the pathogenesis of hypertension in the manner in which OUA differs from DIG and changes the sodium pump gene expression in the arteries and kidneys of rats.

Animals ; Blood Pressure ; drug effects ; Digoxin ; therapeutic use ; Hypertension ; drug therapy ; In Situ Hybridization ; Male ; Ouabain ; therapeutic use ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism

BACKGROUNDOuabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase activity. It also participates in a variety of kinase-mediated signaling pathways associated with Na-K ATPase. Previous studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen (PCNA) plays a coordinating role for numerous proteins involved in multiple processes associated with DNA synthesis. Therefore, we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of hypertension. And PCNA might be involved in this process.

METHODSMale Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control group. Systolic blood pressure was recorded weekly. After four weeks of treatment, morphological changes in the cerebral cortex were analyzed using light and transmission electron microscopy. The expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry, real time quantitative PCR, and Western blotting.

RESULTSAfter 4-week treatment, there was no significant difference in systolic blood pressure compared with the control group, but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain treatment.

CONCLUSIONSThese results suggest that ouabain induces alterations in the brain structure, and this effect is independent of blood pressure. PCNA might be involved in the repair process of ouabain-induced brain damage.

Animals ; Blood Pressure ; drug effects ; Hypertension ; drug therapy ; metabolism ; Immunohistochemistry ; Male ; Ouabain ; therapeutic use ; Proliferating Cell Nuclear Antigen ; metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI).

METHODSFifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope.

RESULTSCompared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a superior effect as compared with the astragaloside group and the SHT low-dose group.

CONCLUSIONSThe SHT effectively alleviated RIRI caused by ischemic reperfusion, promoted the recovery of the polarity of renal tubular epithelial cells, and protected the renal tubules. The therapeutic effects of SHT were superior to those of astragaloside as a single agent.

Acute Disease ; Animals ; Blood Urea Nitrogen ; Cell Adhesion Molecules ; metabolism ; Chromatography, Liquid ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fluorescent Antibody Technique ; Immunoblotting ; Kidney Function Tests ; Kidney Tubules ; blood supply ; drug effects ; enzymology ; pathology ; Low Density Lipoprotein Receptor-Related Protein-2 ; metabolism ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury ; drug therapy ; enzymology ; pathology ; Saponins ; analysis ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Staining and Labeling ; Tablets