Antihypertensive effects of KW-3902, an adenosine A1-receptor antagonist, in Dahl salt-sensitive rats.
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.
Nomura
H
H
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Sizuoka, Japan.
Nagashima
K
K
Kusaka
H
H
Karasawa
A
A
D000818:Animals; D004032:Diet; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014237:Trichlormethiazide / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D004232:Diuretics; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline; D005665:Furosemide; D014237:Trichlormethiazide