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  1. Article: Action of diuretics at the cellular level.

    Greger, R / Lohrmann, E / Schlatter, E

    Clinical nephrology

    1992  Volume 38 Suppl 1, Page(s) S64–8

    Abstract: Classification of diuretics is based on their site and mechanism of action in the nephron. The most ... the loop diuretics (LD); 3. the early distally acting thiazides (TZ); and 4. the K+ sparing diuretics (KS) acting ... diuresis, but a marked attentuation of renal K+ losses. All diuretics act by inhibiting the admission ...

    Abstract Classification of diuretics is based on their site and mechanism of action in the nephron. The most frequently used substances comprise 1. the mostly proximally acting carbonic anhydrase inhibitors (CAI); 2. the loop diuretics (LD); 3. the early distally acting thiazides (TZ); and 4. the K+ sparing diuretics (KS) acting in the distal tubule. CAI such as acetazolamide inhibit the dehydration of H2CO3 at the luminal membrane, the hydration of CO2 within the proximal tubule cell and the exit of HCO-3 out of the cell. As a result of this proximal reabsorption of HCO-3 is reduced, a slight diuresis and saluresis is induced. The enhanced urinary excretion of HCO-3 will cause a metabolic acidosis. LD inhibit the Na+2Cl-K+ carrier in the thick ascending limb of the loop of Henle (TAL). This produces a marked diuresis and saluresis which is accompanied by enhanced Ca2+, Mg2+, K+ and acid excretion. TZ inhibit the Na+Cl- cotransporter in the early distal tubule. The diuresis is less marked than that induced by LD but the renal losses of K+ are comparable. KS inhibit Na+ channels present in the luminal membrane of the cortical collecting tubule. This leads to a very limited diuresis, but a marked attentuation of renal K+ losses. All diuretics act by inhibiting the admission of Na+ (LD, TZ, KS) or HCO-3 (CAI) into the cell. Their organotropy is merely due to the fact that they are concentrated in tubule fluid by volume reabsorption and by proximal tubule secretion.
    MeSH term(s) Animals ; Bicarbonates/metabolism ; Diuretics/pharmacology ; In Vitro Techniques ; Kidney Tubules/drug effects ; Loop of Henle/drug effects ; Mice ; Rabbits ; Rats ; Sodium Channels/drug effects
    Chemical Substances Bicarbonates ; Diuretics ; Sodium Channels
    Language English
    Publishing date 1992
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 185101-9
    ISSN 0301-0430
    ISSN 0301-0430
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  2. Article ; Online: Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

    Lee, Hsiang-Chun / Rudy, Yoram / Po-Yuan, Phd / Sheu, Sheng-Hsiung / Chang, Jan-Gowth / Cui, Jianmin

    Heart rhythm

    2013  Volume 10, Issue 8, Page(s) 1220–1228

    Abstract: ... KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD ... the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action ... ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were ...

    Abstract Background: Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown.
    Objective: To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes.
    Methods: Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol.
    Results: With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram.
    Conclusions: Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia.
    MeSH term(s) Action Potentials/physiology ; Alternative Splicing/genetics ; Amiloride/pharmacology ; Animals ; Blotting, Western ; Delayed Rectifier Potassium Channels/genetics ; Delayed Rectifier Potassium Channels/metabolism ; Diuretics/pharmacology ; Dogs ; Heart Ventricles ; Isoproterenol/pharmacology ; KCNQ1 Potassium Channel/genetics ; KCNQ1 Potassium Channel/metabolism ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances Delayed Rectifier Potassium Channels ; Diuretics ; KCNQ1 Potassium Channel ; Amiloride (7DZO8EB0Z3) ; Isoproterenol (L628TT009W)
    Language English
    Publishing date 2013-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2229357-7
    ISSN 1556-3871 ; 1547-5271
    ISSN (online) 1556-3871
    ISSN 1547-5271
    DOI 10.1016/j.hrthm.2013.04.014
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  3. Article: Comparative mechanisms of action of diuretic drugs in hypertension.

    van Zwieten, P A

    European heart journal

    1992  Volume 13 Suppl G, Page(s) 2–4

    Abstract: This review concerns the modes of action of thiazides, loop- and potassium-sparing diuretics ... Despite detailed knowledge of the renal mode of action of the diuretics, the mechanism whereby they exert ... of aldosterone at the receptor level and impair the reabsorption of Na+ ions and water and their exchange against K+ ions ...

    Abstract This review concerns the modes of action of thiazides, loop- and potassium-sparing diuretics, with particular emphasis on their antihypertensive activity. Thiazide diuretics inhibit an enzyme in the basolateral cell membrane in the distal tubule, thus bringing about an impaired absorption and enhanced excretion of both Na+ and Cl- ions. The loss of Na+ ions is countered by the exchange from Na+ against K+, hence causing a loss of K+ ions. The renal excretion of Ca++ ions is impaired, that of Mg++ ions enhanced. Loop diuretics inhibit a carrier mechanism that enhances the inward transport into the tubular cells of Na+, K+ and Cl- ions as well as water. This process, which occurs in the thick ascending limb of Henle's loop, enhances the urinary excretions of these ions together with water and Ca++ and Mg++ ions. Potassium-sparing diuretics comprise two different categories. Triamterene and amiloride inhibit a local transport mechanism in the distal tubular cells which allows the influx of Na+ and its exchange against K+ or H+ ions. Concomitantly, the excretion of Na+, but not that of K+, ions is enhanced. Aldosterone antagonists inhibit the renal effects of aldosterone at the receptor level and impair the reabsorption of Na+ ions and water and their exchange against K+ ions. Despite detailed knowledge of the renal mode of action of the diuretics, the mechanism whereby they exert their antihypertensive activity is still uncertain. The initial reduction in plasma volume is accompanied by reduction in cardiac output and increased systemic vascular resistance. Continued treatment leads to a return to normal in cardiac output and a reduction in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
    MeSH term(s) Diuretics/pharmacology ; Diuretics/therapeutic use ; Hemodynamics/drug effects ; Humans ; Hypertension/drug therapy ; Hypertension/physiopathology ; Kidney Tubules/drug effects
    Chemical Substances Diuretics
    Language English
    Publishing date 1992-12
    Publishing country England
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/13.suppl_g.2
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  4. Article: Furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases.

    Prandota, Joseph

    American journal of therapeutics

    2002  Volume 9, Issue 4, Page(s) 317–328

    Abstract: ... ouabain-like substances may play an important role in the mechanism of furosemide diuretic action. It was ... of the inhaled steroid. It is proposed that this effect may be explained by the corticosteroid-sparing action ... the plasma levels of circulating endothelin and atrial natriuretic factor (ANF) were significantly elevated ...

    Abstract Accumulated experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in the mechanism of furosemide diuretic action. It was reported that the drug is highly bound in the adrenals, lungs, kidney, spleen, and liver. In patients with liver cirrhosis, furosemide exerted a markedly decreased natriuretic effect compared with normal subjects, and the plasma levels of circulating endothelin and atrial natriuretic factor (ANF) were significantly elevated. In neonates, after administration of furosemide, the urinary excretion of endothelin-1 and aldosterone increased markedly, and it is known that endothelin may release ANF and aldosterone in a dose-dependent manner. Furosemide was used to stimulate zona glomerulosa, whereas ANF decreased the production of steroids in zona glomerulosa and fasciculata cell culture owing to stimulation by various factors. Because the concomitant use of ANF and furosemide appeared to be diuretically effective in newborns after cardiac surgery, one may suggest that furosemide competes with ANF for its effects on the adrenals. Furosemide administered by inhalation exerted a protective effect on allergic and perennial nonallergic rhinitis and was effective in preventing the postsurgical recurrence of nasal polyposis. The drug can also be used as an antiasthmatic agent. In preterm ventilator-dependent infants with chronic lung disease, aerosolized furosemide improved pulmonary function with no marked effect on diuresis. In adults and children with asthma, furosemide exerted a protective effect against bronchoconstriction induced by several indirect stimuli similar to that of disodium cromoglycate or nedocromil. Aerosolized furosemide had a preventive effect also on bronchoconstriction induced by inhaled lysine acetylsalicylate in patients with aspirin-sensitive asthma. In high-dose beclomethasone-dependent asthma, inhaled lysine acetylsalicylate and furosemide exerted a mutually potentiating antiasthmatic activity, allowing considerable sparing of the inhaled steroid. It is proposed that this effect may be explained by the corticosteroid-sparing action of lysine released from the lysine acetylsalicylate molecule because similar beneficial effects were also obtained after the concomitant use of epsilon-aminocaproic acid (whose chemical structure is almost the same as that of lysine) and prednisone. Furosemide exhibited an anti-inflammatory effect through inhibition of production and release of cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha from peripheral mononuclear cells, which may have a beneficial effect on local inflamed tissue imbalance in the ratio of different cytokines, thus improving the sensitivity of target cells to endogenous glucocorticosteroids.
    MeSH term(s) Adult ; Animals ; Asthma/drug therapy ; Child ; Diuretics/metabolism ; Diuretics/pharmacology ; Diuretics/therapeutic use ; Furosemide/metabolism ; Furosemide/pharmacology ; Furosemide/therapeutic use ; Humans ; Infant, Newborn ; Respiratory Tract Diseases/drug therapy ; Rhinitis/drug therapy
    Chemical Substances Diuretics ; Furosemide (7LXU5N7ZO5)
    Language English
    Publishing date 2002-07-12
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1280786-2
    ISSN 1536-3686 ; 1075-2765
    ISSN (online) 1536-3686
    ISSN 1075-2765
    DOI 10.1097/00045391-200207000-00009
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  5. Article: Pharmacological basis of the antihypertensive action of calcium entry blockers.

    van Zwieten, P A / Timmermans, P B

    Journal of cardiovascular pharmacology

    1985  Volume 7 Suppl 4, Page(s) S11–7

    Abstract: ... resistance. At a cellular level this effect is assumed to be induced by the selective inhibition of the slow ... deals with the pharmacological basis of their antihypertensive action, side effects, contraindications ...

    Abstract Calcium entry blockers or calcium antagonists have been recognized as useful antihypertensive drugs, although their definite position in the management of hypertensive disease remains to be established. The present survey deals with the pharmacological basis of their antihypertensive action, side effects, contraindications, and interactions with other drugs. The antihypertensive effect of the various calcium entry blockers is fully explained by arteriolar dilatation, thus leading to a reduction in total peripheral resistance. At a cellular level this effect is assumed to be induced by the selective inhibition of the slow inward current that is carried by calcium ion fluxes. Furthermore, the interaction with vascular postsynaptic alpha 2-adrenoceptor-mediated vasoconstriction may also contribute to vasodilatation.
    MeSH term(s) Adrenergic beta-Antagonists/pharmacology ; Animals ; Antihypertensive Agents ; Blood Circulation/drug effects ; Calcium Channel Blockers/adverse effects ; Calcium Channel Blockers/pharmacology ; Chemical Phenomena ; Chemistry ; Diuretics ; Drug Interactions ; Humans ; In Vitro Techniques ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Rats ; Vascular Resistance/drug effects ; Vasodilator Agents
    Chemical Substances Adrenergic beta-Antagonists ; Antihypertensive Agents ; Calcium Channel Blockers ; Diuretics ; Vasodilator Agents
    Language English
    Publishing date 1985
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 391970-5
    ISSN 1533-4023 ; 0160-2446
    ISSN (online) 1533-4023
    ISSN 0160-2446
    DOI 10.1097/00005344-198507004-00003
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  6. Article: Demonstration of action of muzolimine on the serosal side of Henle's loop cells.

    Faedda, R / Satta, A / Branca, G F / Contu, B / Bartoli, E

    Zeitschrift fur Kardiologie

    1985  Volume 74 Suppl 2, Page(s) 166–170

    Abstract: ... UNa rose in the left post-obstructed kidney and reached a plateau level by the 3rd to 5th sample ... on frog skin, it is believed that muzolimine acts from the serosal cell side, unlike all other diuretics ... We decided to assess the site of action of muzolimine (mucosa versus serosa) by experiments on rats ...

    Abstract Muzolimine, a new diuretic, is known to act by inhibiting Na transport along the ascending limb of Henle's loop. Because of its ineffectiveness when perfused into the lumen, and as a result of experiments on frog skin, it is believed that muzolimine acts from the serosal cell side, unlike all other diuretics. We decided to assess the site of action of muzolimine (mucosa versus serosa) by experiments on rats. The animals were anesthetized, both ureters cannulated, and a hydronephrosis established in the left kidney by applying a counterpressure to the ureter, slowly and progressively increased up to 60 cm H2O in 3 minutes and kept stable for 20 minutes. Then either muzolimine 1.2 mg, or furosemide 4 mg, was injected i.v. together with 131I-Hypaque as a glomerular marker. Three minutes later the hydronephrosis was released in the left kidney by cutting the catheter, and urine collections were started simultaneously in both kidneys into 25 microliter glass capillaries, that were filled in continuous sequence and numbered progressively. In each urine sample from each glass capillary Na and 131I-Hypaque were measured. In 5 animals receiving furosemide, UNa rose in the left post-obstructed kidney and reached a plateau level by the 3rd to 5th sample. The rise in Na concentration, indicating delivery of urine whose Na reabsorption had been inhibited along the loop of Henle paralleled that in 131I-Hypaque, indicating that the diuretic and the glomerular marker had reached Henle's loop simultaneously, following filtration after the hydronephrosis had been discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)
    MeSH term(s) Animals ; Furosemide/pharmacology ; Glomerular Filtration Rate ; Iodine Radioisotopes ; Kidney/cytology ; Kidney Tubules/drug effects ; Loop of Henle/drug effects ; Muzolimine/pharmacology ; Pyrazoles/pharmacology ; Rats
    Chemical Substances Iodine Radioisotopes ; Pyrazoles ; Muzolimine (07Z36289ZX) ; Furosemide (7LXU5N7ZO5)
    Language English
    Publishing date 1985
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 124481-4
    ISSN 1435-1285 ; 0300-5860
    ISSN (online) 1435-1285
    ISSN 0300-5860
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  7. Article ; Online: 8-Aminoguanine and Its Actions on Renal Excretory Function.

    Jackson, Edwin K / Gillespie, Delbert G / Mi, Zaichuan

    Hypertension (Dallas, Tex. : 1979)

    2023  Volume 80, Issue 5, Page(s) 981–994

    Abstract: ... increased renal microdialysate levels of inosine and guanosine. Intrarenal inosine, but not guanosine ... by increasing renal interstitial levels of inosine which, via A ... knockout rats, laser doppler blood flow analysis, cultured renal microvascular smooth muscle cells, HEK293 ...

    Abstract Background: The endogenous purine 8-aminoguanine induces diuresis/natriuresis/glucosuria by inhibiting PNPase (purine nucleoside phosphorylase); however, mechanistic details are unknown.
    Methods: Here, we further explored in rats 8-aminoguanine's effects on renal excretory function by combining studies using intravenous 8-aminoguanine, intrarenal artery infusions of PNPase substrates (inosine and guanosine), renal microdialysis, mass spectrometry, selective adenosine receptor ligands, adenosine receptor knockout rats, laser doppler blood flow analysis, cultured renal microvascular smooth muscle cells, HEK293 cells expressing A
    Results: Intravenous 8-aminoguanine caused diuresis/natriuresis/glucosuria and increased renal microdialysate levels of inosine and guanosine. Intrarenal inosine, but not guanosine, exerted diuretic/natriuretic/glucosuric effects. In 8-aminoguanine-pretreated rats, intrarenal inosine did not induce additional diuresis/natriuresis/glucosuria. 8-Aminoguanine did not induce diuresis/natriuresis/glucosuria in A
    Conclusions: 8-Aminoguanine induces diuresis/natriuresis/glucosuria by increasing renal interstitial levels of inosine which, via A
    MeSH term(s) Rats ; Humans ; Animals ; Adenylyl Cyclases/pharmacology ; HEK293 Cells ; Diuresis ; Diuretics/pharmacology ; Natriuresis ; Receptors, Purinergic P1 ; Inosine/pharmacology
    Chemical Substances 8-aminoguanine (28128-41-8) ; Adenylyl Cyclases (EC 4.6.1.1) ; Diuretics ; Receptors, Purinergic P1 ; Inosine (5A614L51CT)
    Language English
    Publishing date 2023-02-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.122.20760
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  8. Article: Cardiac cellular actions of hydrochlorothiazide.

    Galán, L / Ferrer, T / Artiles, A / Talavera, K / Salinas, E / Orta, G / García-Barreto, D / Alvarez, J L

    Fundamental & clinical pharmacology

    2001  Volume 15, Issue 1, Page(s) 9–17

    Abstract: ... about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and ... and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast ... In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure ...

    Abstract In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.
    MeSH term(s) Action Potentials/drug effects ; Animals ; Calcium/metabolism ; Diuretics ; Dose-Response Relationship, Drug ; Electrophysiology ; Heart/drug effects ; Heart/physiology ; Heart Conduction System/drug effects ; Heart Conduction System/physiology ; Heart Ventricles/drug effects ; Hydrochlorothiazide/pharmacology ; In Vitro Techniques ; Membrane Potentials/drug effects ; Muscle, Smooth/cytology ; Muscle, Smooth/drug effects ; Myocardial Contraction/drug effects ; Myocardium/cytology ; Patch-Clamp Techniques ; Potassium Channels/drug effects ; Rats ; Sodium/metabolism ; Sodium Chloride Symporter Inhibitors/pharmacology ; Stimulation, Chemical
    Chemical Substances Diuretics ; Potassium Channels ; Sodium Chloride Symporter Inhibitors ; Hydrochlorothiazide (0J48LPH2TH) ; Sodium (9NEZ333N27) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2001-08-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639134-5
    ISSN 1472-8206 ; 0767-3981
    ISSN (online) 1472-8206
    ISSN 0767-3981
    DOI 10.1046/j.1472-8206.2001.00009.x
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  9. Article ; Online: Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet.

    Jin, Chunhua / O'Boyle, Sean / Kleven, Daniel T / Pollock, Jennifer S / Pollock, David M / White, John J

    Clinical and experimental pharmacology & physiology

    2014  Volume 41, Issue 8, Page(s) 579–588

    Abstract: ... unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects ... monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice ... with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells ...

    Abstract Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/pharmacology ; Antihypertensive Agents/pharmacology ; Arterial Pressure/drug effects ; Benzimidazoles/pharmacology ; Chlorthalidone/pharmacology ; Diet, High-Fat ; Drug Therapy, Combination/methods ; Inflammation/drug therapy ; Kidney/drug effects ; Male ; Oxadiazoles/pharmacology ; Rats ; Rats, Inbred Dahl ; Sodium Chloride, Dietary/administration & dosage
    Chemical Substances Anti-Inflammatory Agents ; Antihypertensive Agents ; Benzimidazoles ; Oxadiazoles ; Sodium Chloride, Dietary ; azilsartan (F9NUX55P23) ; Chlorthalidone (Q0MQD1073Q)
    Language English
    Publishing date 2014-08
    Publishing country Australia
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 189277-0
    ISSN 1440-1681 ; 0305-1870 ; 0143-9294
    ISSN (online) 1440-1681
    ISSN 0305-1870 ; 0143-9294
    DOI 10.1111/1440-1681.12250
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Molecular actions of diuretics.

    Heidenreich, O / Greven, J / Heintze, K

    Klinische Wochenschrift

    1982  Volume 60, Issue 19, Page(s) 1258–1263

    Abstract: ... distal tubule and in the collecting duct. On the molecular level diuretics do not inhibit Na+-K+-ATPase ... The criteria upon which diuretics are classified is based upon their site of action ... within the nephron. Carboanhydrase inhibitors act in the proximal tubule, high-ceiling diuretics in the ascending ...

    Abstract The criteria upon which diuretics are classified is based upon their site of action within the nephron. Carboanhydrase inhibitors act in the proximal tubule, high-ceiling diuretics in the ascending loop of Henle, the thiazides in the early distal tubule and the potassium-sparing diuretics in the late distal tubule and in the collecting duct. On the molecular level diuretics do not inhibit Na+-K+-ATPase but interfere with the permeability of the tubule membranes or transport systems for certain ions and thus also influence the potential differences in the different parts of the nephron. Since carboanhydrase is located in the proximal tubule cells, not only in the cytosol but also in the brushborders and in the peritubular membranes, acetazolamide and other carboanhydrase inhibitors act on three different sites in these cells. The loop diuretics inhibit the secondary active chloride reabsorption. The receptors in this part of the nephron are stereospecific. Only the levorotatory isomere of ozolinone has active diuretic properties whereas the dextrorotatory isomere does not. Perfusion experiments of the loop of Henle with different lectins give evidence that glycoproteins containing alpha-1-fucose are involved in the reabsorption of Na+ and Cl-. Experiments on the isolated stripped rabbit colon under the condition of chloride secretion reveal striking similarities between the receptors for chloride reabsorption in the luminal cell membranes of the ascending loop of Henle and in the serosal cell membranes of the colon. The potassium-sparing diuretics amiloride and triamterene act by blocking sodium channels in the distal parts of the nephron. Thus the lumen negative potential difference decreases and (passive) potassium secretion is diminished.
    MeSH term(s) Acetazolamide/pharmacology ; Animals ; Carbonic Anhydrase Inhibitors/pharmacology ; Chlorides/urine ; Diuretics/pharmacology ; Humans ; Kidney Tubules, Distal/drug effects ; Loop of Henle/drug effects ; Nephrons/drug effects ; Rats ; Sodium/urine ; Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors
    Chemical Substances Carbonic Anhydrase Inhibitors ; Chlorides ; Diuretics ; Sodium (9NEZ333N27) ; Sodium-Potassium-Exchanging ATPase (EC 3.6.3.9) ; Acetazolamide (O3FX965V0I)
    Language English
    Publishing date 1982-10-01
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 200457-4
    ISSN 0023-2173
    ISSN 0023-2173
    DOI 10.1007/bf01716734
    Database MEDical Literature Analysis and Retrieval System OnLINE

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