Antihypertensive Effects of KW-3902, an Adenosine A₁-Receptor Antagonist, in Dahl Salt-Sensitive Rats

抄録

We determined the effects of KW-3902 (8-(noradamantan-3-yl)-1, 3-dipropylxanthine), a novel adenosine A₁-receptor antagonist, on the development of hypertension in Dahl salt-sensitive (Dahl-S) rats. KW-3902 (0.00017% w/w-0.017% w/w), fed with the diet, prevented the development of hypertension at 2-6 weeks in response to the high (8% w/w) NaCl diet. KW-3902 increased urine volume and sodium excretion and attenuated cardiac hypertrophy. In another series of the experiments employing the clearance method, KW-3902 (0.1 mg/kg, i.v.) increased urine volume, sodium excretion and lithium clearance in anesthetized Dahl-S rats. These results suggest that the antihypertensive effect of KW-3902 in Dahl-S rats is mediated via its natriuretic effect, the site of action being, at least partly, the proximal tubule. The adenosine A₁-receptor antagonist may be effective for the treatment of salt-sensitive hypertension.