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The Journal of Pharmacology and... Jan 2014The renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical...
The renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct, plays an important role in kidney physiology by regulating salt reabsorption. Loss-of-function mutations in the human ROMK channel are associated with antenatal type II Bartter's syndrome, an autosomal recessive life-threatening salt-wasting disorder with mild hypokalemia. Similar observations have been reported from studies with ROMK knockout mice and rats. It is noteworthy that heterozygous carriers of Kir1.1 mutations associated with antenatal Bartter's syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. Although selective ROMK inhibitors would be expected to represent a new class of diuretics, this hypothesis has not been pharmacologically tested. Compound A [5-(2-(4-(2-(4-(1H-tetrazol-1-yl)phenyl)acetyl)piperazin-1-yl)ethyl)isobenzofuran-1(3H)-one)], a potent ROMK inhibitor with appropriate selectivity and characteristics for in vivo testing, has been identified. Compound A accesses the channel through the cytoplasmic side and binds to residues lining the pore within the transmembrane region below the selectivity filter. In normotensive rats and dogs, short-term oral administration of compound A caused concentration-dependent diuresis and natriuresis that were comparable to hydrochlorothiazide. Unlike hydrochlorothiazide, however, compound A did not cause any significant urinary potassium losses or changes in plasma electrolyte levels. These data indicate that pharmacologic inhibition of ROMK has the potential for affording diuretic/natriuretic efficacy similar to that of clinically used diuretics but without the dose-limiting hypokalemia associated with the use of loop and thiazide-like diuretics.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Diuresis; Dogs; Dose-Response Relationship, Drug; Female; HEK293 Cells; Humans; Madin Darby Canine Kidney Cells; Male; Natriuresis; Potassium Channel Blockers; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley
PubMed: 24142912
DOI: 10.1124/jpet.113.208603 -
Materia Medica Polona. Polish Journal... 1990The present article aimed to study the intactness of the physiological mechanism of ANP secretion in 64 kidney transplant patients treated with cyclosporine A +... (Comparative Study)
Comparative Study
UNLABELLED
The present article aimed to study the intactness of the physiological mechanism of ANP secretion in 64 kidney transplant patients treated with cyclosporine A + prednisone (CyA group--35 patients) or azathioprine + prednisone + promethasine respectively (Aza group or--29 patients). The control group comprised 15 healthy persons. ANP plasma levels were assessed before and 1 h and 2 h after neck out water immersion (WI). Higher basal ANP levels were found in patients of the CyA and Aza group than in normals (significantly higher in patients of the CyA group). WI induced an increase of plasma volume (PV) which was of comparable magnitude in all examined groups. It was accompanied by a significant increase of plasma ANP, diuresis and of natriuresis, which was significantly lower in transplanted patients than in normals. Only in healthy persons a significant positive correlation was found between the WI induced increase of plasma ANP and diuresis and natriuresis respectively.
CONCLUSIONS
1) kidney transplant patients are characterized by an intact, although reduced response of ANP secretion, diuresis and natriuresis to central hypervolaemia; 2) WI induced increase of diuresis and natriuresis does not seem to be only dependent upon ANP secretion in kidney transplant patients; 3) kind of immunosuppressive therapy seems to be of importance in the pathogenesis of altered ANP secretion in kidney transplant patients.
Topics: Adult; Atrial Natriuretic Factor; Diuresis; Humans; Immersion; Kidney Transplantation; Natriuresis; Water
PubMed: 2151903
DOI: No ID Found -
The American Journal of Physiology Oct 1957
Topics: Animals; Diuresis; Rats
PubMed: 13478682
DOI: 10.1152/ajplegacy.1957.191.1.45 -
Deutsche Medizinische Wochenschrift... Oct 1972
Topics: Diuresis; Furosemide; Humans
PubMed: 5083095
DOI: No ID Found -
Revista Clinica Espanola Sep 1959
Topics: Acetazolamide; Diuresis; Hypertonic Solutions
PubMed: 14423978
DOI: No ID Found -
Surgical Forum 1958
Topics: Animals; Cardiovascular System; Diuresis; Dogs; Portacaval Shunt, Surgical; Portal System; Veins
PubMed: 13635445
DOI: No ID Found -
Giornale Di Clinica Medica Oct 1959
Topics: Biological Transport; Diuresis; Homeostasis; Serotonin
PubMed: 13793106
DOI: No ID Found -
The American Journal of Physiology May 1957
Topics: Animals; Blood Pressure; Blood Pressure Determination; Capillaries; Diuresis; Kidney; Pressure; Punctures; Rats
PubMed: 13435366
DOI: 10.1152/ajplegacy.1957.189.2.323 -
Nederlands Tijdschrift Voor Geneeskunde Apr 1965
Topics: Chlorothiazide; Diabetes Insipidus; Diuresis; Humans; Natriuresis
PubMed: 14325607
DOI: No ID Found -
Arztliche Wochenschrift Jan 1957
Topics: Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Diuresis; Diuretics; Hydro-Lyases
PubMed: 13402607
DOI: No ID Found