Vasorelaxant actions of 5-OH-indapamide, a major metabolite of indapamide: comparison with indapamide, hydrochlorothiazide and cicletanine. 1994

J A Calder, and M Schachter, and P S Sever
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.

5-OH-Indapamide is a principal metabolite of indapamide, and possesses similar antihypertensive and diuretic properties. This study investigated the mechanisms of the acute vasodilator actions of 5-OH-indapamide, indapamide, hydrochlorothiazide and cicletanine and their interaction with ion channels in isolated guinea pig mesenteric arteries. Hydrochlorothiazide, cicletanine and 5-OH-indapamide relaxed noradrenaline-constricted vessels significantly more than K(+)-constricted vessels (P < 0.001) and the relaxations were reduced in the presence of charybdotoxin (P < 0.001). 5-OH-Indapamide-induced relaxation was reduced (by 42% at 30 microM) by glibenclamide (P < 0.001). Hydrochlorothiazide, cicletanine and 5-OH-indapamide (all at 10 microM) were weak Ca2+ antagonists shifting the Ca2+ dose-response curves half a log unit to the right (P < 0.01). Indapamide was a more potent inhibitor, a 10 microM concentration shifting the Ca2+ dose-response curve three log units to the right and reducing maximal-induced Ca2+ contraction by 72% (P < 0.001). Hydrochlorothiazide, cicletanine and 5-OH-indapamide-induced relaxations appear to be partly mediated via Ca(2+)-activated K+ channels; 5-OH-Indapamide-induced relaxation is also partly mediated via ATP-sensitive K+ channels. Indapamide is a potent Ca2+ antagonist.

UI MeSH Term Description Entries
D007190 Indapamide A benzamide-sulfonamide-indole derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS. Metindamide,S-1520,SE-1520,S 1520,S1520,SE 1520,SE1520
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D004576 Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Electromyogram,Surface Electromyography,Electromyograms,Electromyographies,Electromyographies, Surface,Electromyography, Surface,Surface Electromyographies
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006852 Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Dichlothiazide,Dihydrochlorothiazide,Esidrex,Esidrix,HCTZ,HydroDIURIL,Hypothiazide,Oretic,Sectrazide

Related Publications

J A Calder, and M Schachter, and P S Sever
September 1988, Pharmacological research communications,
J A Calder, and M Schachter, and P S Sever
January 1993, Journal of cardiovascular pharmacology,
J A Calder, and M Schachter, and P S Sever
May 1993, Naunyn-Schmiedeberg's archives of pharmacology,
J A Calder, and M Schachter, and P S Sever
November 1989, Archives des maladies du coeur et des vaisseaux,
J A Calder, and M Schachter, and P S Sever
July 2012, Expert opinion on pharmacotherapy,
J A Calder, and M Schachter, and P S Sever
April 2012, Journal of hypertension,
J A Calder, and M Schachter, and P S Sever
July 2002, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde,
Copied contents to your clipboard!