Possible involvement of aminopeptidase A in hypertension and renal damage in Dahl salt-sensitive rats.
BACKGROUND
Although aminopeptidase A (APA), which is abundant in the kidneys, is responsible for metabolizing angiotensin II (Ang II), its association with salt sensitivity remains uncertain. We aimed to clarify the involvement of APA in salt-induced hypertension and renal damage.


METHODS
Male Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats were fed low-salt (0.3%) or high-salt diet (8%) from 6 weeks of age for 12 weeks. Tail-cuff-measured blood pressure (BP), renal APA activity, renal Ang II levels, histologic renal damage, and APA immunoreactivity were periodically examined.


RESULTS
Systolic BP progressively increased only in DS rats given the high-salt diet (DS-8% rats). The DR-8% rats had approximately 3-fold higher renal APA activity than the rats given the low-salt diet (DR-0.3% rats) during the maintenance on the high-salt diet. However, although DS-8% rats also had 2.5-fold higher renal APA activity than DS-0.3% rats at 10 weeks, continuing the high-salt diet afterward suppressed the activity in DS-8% rats below the levels observed in DS-0.3% rats. High-salt diet reduced renal Ang II levels by 30% in DR rats, whereas it showed a small and nonsignificant decrease in DS rats. The number of injured glomeruli was markedly elevated in DS-8% rats after 10 weeks. The APA immunostaining in DS-8% rats was enhanced in glomeruli displaying mild damage, diminished in the severely injured glomeruli, and absent in lesions with hyalinization.


CONCLUSIONS
High-salt diet in DS rats increased renal APA activity, although renal injury remained mild, but then reduced it along with the progression of glomerulosclerosis, suggesting that reduced APA activity may be involved in the deterioration of salt-induced hypertension and renal injury.
Nomura
Mami
M
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nomura
Seiji
S
Mitsui
Takashi
T
Suzuki
Masaki
M
Kobayashi
Honami
H
Ito
Tomomi
T
Itakura
Atsuo
A
Kikkawa
Fumitaka
F
Mizutani
Shigehiko
S
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000503:physiopathology; D043384:Glutamyl Aminopeptidase / Q000378:metabolism*; D006818:Hyalin / Q000378:metabolism; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D012720:Severity of Illness Index; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D013194:Staining and Labeling
D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D043384:Glutamyl Aminopeptidase