A NEW ADENOSINE SUBTYPE-1 RECEPTOR ANTAGONIST, FK-838, ATTENUATES SALT-INDUCED HYPERTENSION IN DAHL SALT-SENSITIVE RATS

We investigated the effects of the adenosine type-1 receptor antagonis t 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 atte nuated the development of hypertension in Dahl S rats, and caused a de crease in aortic weight in a dose dependent fashion. The adenosine ant agonist did not produce any detectable metabolic disturbance. The bloo d pressure reduction by FK-838 was associated with attenuation of glom erular and arterial injury in the kidney. The renal protective effect of FK-838 treatment was associated with a reduction of plasma renin ac tivity 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 adeno sine Al receptor antagonism reduces salt-induced hypertension and the consequent renal injuries.