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.
Y Uehara  1 ,  A Numabe ,  N Hirawa ,  Y Kawabata ,  H Nagoshi ,  H Kaneko ,  T Gomi ,  A Goto ,  T Toyo-oka ,  M Omata
Affiliations
  • 1. 2nd Department of Medicine, University of Tokyo, Japan.
PMID: 8998253 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.

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