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 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.
Uehara
Y
Y
2nd Department of Medicine, University of Tokyo, Japan.
Numabe
A
A
Hirawa
N
N
Kawabata
Y
Y
Nagoshi
H
H
Kaneko
H
H
Gomi
T
T
Goto
A
A
Toyo-oka
T
T
Omata
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D015777:Eicosanoids / Q000652:urine; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D009929:Organ Size / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride
D000959:Antihypertensive Agents; D015777:Eicosanoids; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011725:Pyridines; D006852:Hydrochlorothiazide; C102861:FK 838; D012965:Sodium Chloride; D003404:Creatinine