Involvement of angiotensin II in development of spontaneous nephrosis in Dahl salt-sensitive rats.
We investigated the effect of angiotensin-converting enzyme inhibition on spontaneous nephrosis in Dahl salt-sensitive (Dahl/S) rats. Dahl/S rats fed on a normal sodium diet spontaneously developed nephrosis and mild hypertension from a young age. In young Dahl/S rats, an angiotensin-converting enzyme inhibitor, imidapril, attenuated the development of proteinuria accompanied by a decrease in blood pressure. Methylprednisolone, a potent therapeutic agent for proteinuria, did not affect the development of nephrosis. An angiotensin AT1 receptor antagonist, losartan, but not a Ca2+ channel blocker, verapamil, inhibited the development of nephrosis while both agents decreased blood pressure to a similar extent as imidapril. In mature Dahl/S rats, imidapril suppressed not only the development of proteinuria but also the glomerular lesions. It is concluded that the development of spontaneous nephrosis in Dahl/S rats is mediated by angiotensin II.
Yoneda
H
H
Discovery Research Laboratory, Tanabe Seiyaku, Saitama, Japan. yoneda-h@tanabe.co.jp
Toriumi
W
W
Ohmachi
Y
Y
Okumura
F
F
Fujimura
H
H
Nishiyama
S
S
D000375:Aging / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D009401:Nephrosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary; D014700:Verapamil / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D005938:Glucocorticoids; D007093:Imidazoles; D048289:Imidazolidines; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D002784:Cholesterol; C065166:imidapril; D014700:Verapamil; D019808:Losartan; D008775:Methylprednisolone