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

Am J Hypertens. 1995 Dec;8(12 Pt 1):1189-99. doi: 10.1016/0895-7061(95)00253-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacokinetics
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Body Weight / drug effects
  • Creatinine / urine
  • Eicosanoids / urine
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Function Tests
  • Organ Size / drug effects
  • Purinergic P1 Receptor Antagonists*
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / therapeutic use*
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Rats
  • Rats, Inbred Strains
  • Sodium Chloride

Substances

  • Antihypertensive Agents
  • Eicosanoids
  • Purinergic P1 Receptor Antagonists
  • Pyrazoles
  • Pyridines
  • Hydrochlorothiazide
  • FK 838
  • Sodium Chloride
  • Creatinine