Mechanistic analysis of renal protection by angiotensin converting enzyme inhibitor in Dahl salt-sensitive rats.
OBJECTIVE
To investigate whether and how renin-angiotensin inhibition attenuates renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl-S) rats.


METHODS
Dahl-S rats fed a high-salt (4% sodium chloride) diet for 6 weeks were treated with the angiotensin converting enzyme (ACE) inhibitor alacepril or the angiotensin receptor antagonist losartan for 4 weeks. Functional and morphological alterations in the kidney were investigated.


RESULTS
Alacepril decreased systolic blood pressure (SBP). This SBP reduction was associated with the attenuation of cardiac and aortic wall hypertrophy and that of proteinuria and urinary N-acetyl-beta-D-glucosaminidase excretion. Kidney injuries, e.g. glomerular, arterial and tubular damage, were improved with alacepril treatment. Losartan decreased SBP to the same extent as alacepril, but neither renal function nor morphological structure was improved as was the case with alacepril. The response of the renal eicosanoid system to alacepril was inadequate, but cyclic GMP excretion, an indicator of nitric oxide formation, was significantly enhanced and lipid peroxidation in the kidney was decreased.


CONCLUSIONS
The beneficial effects of ACE inhibition on the renal injury in Dahl-S rats outrange those induced by the receptor antagonism. This might be due to multiple factors including an increased vasodepressor eicosanoid system, enhanced nitric oxide formation and possible inhibition of oxygen radical generation in the injured renal tissues.
Hirawa
N
N
Department of Nephrology, Kantoh-Teishin Hospital, Tokyo, Japan.
Uehara
Y
Y
Kawabata
Y
Y
Ohshima
N
N
Ono
H
H
Nagata
T
T
Gomi
T
T
Ikeda
T
T
Goto
A
A
Yagi
S
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D019808:Losartan; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology; D014556:Urine / Q000737:chemistry
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D012965:Sodium Chloride; D002216:Captopril; D019808:Losartan; C046835:alacepril