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A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced hypertension in Dahl salt-sensitive rats.

Abstract
We investigated the effects of the adenosine type-1 receptor antagonist FK-838 on salt-induced hypertension in Dahl-Sea salt-sensitive (Dahl S) rats. Dahl S rats fed a high-salt (4% NaCl) diet for 4 weeks were treated with FK-838 or hydrochlorothiazide for 4 weeks and alterations in kidney function and morphologic changes were assessed. FK-838 attenuated the development of hypertension in Dahl S rats, and caused a decrease in aortic weight in a dose dependent fashion. The adenosine antagonist did not produce any detectable metabolic disturbance. The blood pressure reduction by FK-838 was associated with attenuation of glomerular and arterial injury in the kidney. The renal protective effect of FK-838 treatment was associated with a reduction of plasma renin activity and plasma aldosterone concentration. In contrast, the thiazide diuretic, which produced almost the same blood pressure reduction as FK-838, did not attenuate renal damage. These data indicate that adenosine A1 receptor antagonism reduces salt-induced hypertension and the consequent renal injuries.
AuthorsY Uehara, A Numabe, N Hirawa, Y Kawabata, H Nagoshi, H Kaneko, T Gomi, A Goto, T Toyo-oka, M Omata
JournalAmerican journal of hypertension (Am J Hypertens) Vol. 8 Issue 12 Pt 1 Pg. 1189-99 (Dec 1995) ISSN: 0895-7061 [Print] United States
PMID8998253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antihypertensive Agents
  • Eicosanoids
  • Purinergic P1 Receptor Antagonists
  • Pyrazoles
  • Pyridines
  • Hydrochlorothiazide
  • FK 838
  • Sodium Chloride
  • Creatinine
Topics
  • Animals
  • Antihypertensive Agents (pharmacokinetics, therapeutic use)
  • Blood Pressure (drug effects, physiology)
  • Body Weight (drug effects)
  • Creatinine (urine)
  • Eicosanoids (urine)
  • Hydrochlorothiazide (therapeutic use)
  • Hypertension (chemically induced, drug therapy, genetics)
  • Kidney (metabolism, pathology)
  • Kidney Function Tests
  • Organ Size (drug effects)
  • Purinergic P1 Receptor Antagonists
  • Pyrazoles (pharmacokinetics, therapeutic use)
  • Pyridines (pharmacokinetics, therapeutic use)
  • Rats
  • Rats, Inbred Strains
  • Sodium Chloride

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