Nonpeptide angiotensin II type 1 receptor antagonist prevents nephrosclerosis in hypertensive rats.
Angiotensin II (AII) appears essential in remnant kidney models of renal injury in rats, and renal injury was reduced by angiotensin-converting enzyme inhibitor (ACEI). To determine whether this is due to AII blockade or other actions of ACEI, we studied a nonpeptide AII type 1 receptor antagonist and an ACEI in partially nephrectomised spontaneously hypertensive rats (SHR). Thirty SHR underwent surgery and were divided into three equal groups: Control, TCV (0.5 mg/kg/day TCV-116), and CAP (30 mg/kg/day captopril). All SHR received a 5%-NaCl diet. Systolic blood pressure (SBP) and urinary protein were measured at 2-week intervals. Serum total protein, albumin, urea nitrogen, and creatinine were determined at week 8. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured at weeks 4 and 8. Renal injury was evaluated histopathologically. TCV and CAP reduced SBP at week 2 and proteinuria at week 8. GFR and RBF fell in all groups, but decreases were not significant in treated SHR and histopathological changes were significantly ameliorated. All blockade by TCV or CAP reduces renal injury in salt-loaded SHR with partial renal ablation. AII is essential in remnant kidney models of renal injury, and AII blockade is essential in renal protection by ACEI.
Kanno
Y
Y
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Okada
H
H
Suzuki
H
H
Ikenaga
H
H
Saruta
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000150:complications* / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000601:surgery; D009392:Nephrectomy; D009400:Nephrosclerosis / Q000517:prevention & control*; D011355:Prodrugs / Q000627:therapeutic use*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011355:Prodrugs; D013777:Tetrazoles; D002216:Captopril; C077793:candesartan cilexetil