Differential effects of transient treatment of spontaneously hypertensive rats with various antihypertensive agents on the subsequent development of diabetic nephropathy.
OBJECTIVE
We have previously shown that treatment of spontaneously hypertensive rats (SHR) with an angiotensin receptor blocker (ARB) during the 'critical period' from age 3 to 10 weeks confers protection against L-NAME-induced renal injury later in life. The aim of this study was to examine the effects of transient prepubertal exposure to ARB on the development of nephropathy in streptozotocin-induced diabetic SHR and to compare the results with other antihypertensive agents including a mineralocorticoid receptor antagonist (MR-ant).


METHODS
Male SHR (n = 43) were transiently treated with candesartan (ARB), potassium canreonate (the active metabolite of the MR-ant spironolactone) or hydralazine (vasodilator) between 3 and 10 weeks of age with untreated rats serving as controls. An additional group was treated continuously with candesartan throughout the study. Rats were injected with streptozotocin to induce diabetes at age 16 weeks and followed until age 8 months.


RESULTS
Diabetic control rats showed signs of diabetic nephropathy including albuminuria and mesangial expansion. These changes were significantly suppressed in rats exposed to ARB or MR-ant. Systolic blood pressure was significantly reduced compared to controls in the ARB (transient) and ARB (sustained) groups, but not in the MR-ant or vasodilator groups.


CONCLUSIONS
Transient prepubertal exposure to ARB or MR-ant, but not vasodilator, confers protection against the later development of diabetic nephropathy and involves blood pressure-independent protective mechanisms.
Ishiguro
Kimiko
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Sasamura
Hiroyuki
H
Sakamaki
Yusuke
Y
Hayashi
Kaori
K
Saruta
Takao
T
Itoh
Hiroshi
H
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D006973:Hypertension / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D016896:Treatment Outcome
D000959:Antihypertensive Agents