Diuretic effects of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized dogs. 1994

T Yamagata, and T Kobayashi, and H Kusaka, and A Karasawa
Department of Pharmacology, Pharmaceutical Research Laboratories, Kogyo Co., Ltd., Shizuoka, Japan.

The effects of intravenous infusion of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), a novel adenosine A1-receptor antagonist, on urine volume, urinary excretion of electrolytes and renal hemodynamics were examined in anesthetized dogs. KW-3902 at 10 and 30 micrograms/kg/min for 20 min inhibited the decline of renal blood flow induced by intrarenal arterial injection of adenosine (0.5-2.0 micrograms). KW-3902 at these doses produced significant increases in urine volume and sodium excretion with little change in potassium excretion. The diuretic effect of KW-3902 at 30 micrograms/kg/min for 20 min continued for longer than 1 h even after discontinuation of the KW-3902 infusion. KW-3902 did not affect creatinine clearance, renal blood flow, arterial blood pressure or heart rate. Furosemide at 10 micrograms/kg/min for 20 min brought about significant increases in urine volume and excretion of sodium and potassium. The diuresis and saliuresis induced by furosemide continued for only 40 min after discontinuation of the drug infusion. Trichlormethiazide at 3 micrograms/kg/min for 20 min also provoked increases in urine volume and sodium excretion, but did not affect potassium excretion. The diuretic and natriuretic effect of trichlormethiazide gradually disappeared after discontinuation of the drug infusion. The present study in anesthetized dogs suggests that KW-3902, an adenosine A1-receptor antagonist, produces diuresis and natriuresis but not kaliuresis and that the diuresis and natriuresis are caused in large part by the inhibition of sodium reabsorption at tubular sites.

UI MeSH Term Description Entries
D008297 Male Males
D012079 Renal Circulation The circulation of the BLOOD through the vessels of the KIDNEY. Kidney Circulation,Renal Blood Flow,Circulation, Kidney,Circulation, Renal,Blood Flow, Renal,Flow, Renal Blood
D004232 Diuretics Agents that promote the excretion of urine through their effects on kidney function. Diuretic,Diuretic Effect,Diuretic Effects,Effect, Diuretic,Effects, Diuretic
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004573 Electrolytes Substances that dissociate into two or more ions, to some extent, in water. Solutions of electrolytes thus conduct an electric current and can be decomposed by it (ELECTROLYSIS). (Grant & Hackh's Chemical Dictionary, 5th ed) Electrolyte
D005260 Female Females
D005665 Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY. Frusemide,Fursemide,Errolon,Frusemid,Furanthril,Furantral,Furosemide Monohydrochloride,Furosemide Monosodium Salt,Fusid,Lasix
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000758 Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.

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