High salt intake potentiates the renal vascular and glomerular damage caused by low doses of angiotensin II in uni-nephrectomized rats.
OBJECTIVE
We recently reported that the renin-angiotensin system plays an important role in the progression of vascular and kidney injuries, even in Dahl salt-sensitive rats with volume-dependent hypertension. In this study, we investigated whether a high-salt diet increases susceptibility to kidney injury induced by angiotensin II in normotensive, uni-nephrectomized Sprague-Dawley rats, which mimics the condition of salt-volume repletion and blunted renin-angiotensin system.


METHODS
The rats were fed either a low-salt (0.3% NaCl) or a high-salt (4% NaCl) diet and divided into five groups: two control groups with a low-salt or a high-salt diet without angiotensin II infusion (saline infusion), and three angiotensin II groups (angiotensin II infusion, 10 or 50 ng/kg per min with high-salt diet, 50 ng/kg per min with low-salt diet, subcutaneously). The rats were kept on these regimes for 8 weeks. The blood pressure was measured every week. Functional and morphological alterations in the kidney were assessed at the end of the experiment


RESULTS
There were no differences in the arterial blood pressures of the five experimental groups. However, angiotensin II infusion increased the weights of the heart and aortic walls in a dose-dependent manner in the high-salt groups. There was also a dose-dependent increase in proteinuria, N-acetyl-beta-D-glucosaminidase activity (NAG) excretion, and additional glomerular and arterial injuries in the kidney, associated with angiotensin II infusion in the high-salt groups. In the rats given a higher dose of angiotensin II, the high-salt diet significantly increased the weights of the heart and aortic walls and exacerbated the renal function and morphological injuries, compared to the low-salt group. High-salt diet alone increased the kidney and heart weights. However, it did not significantly influence the results of the morphological and functional study. On the other hand, angiotensin II infusion on a low-salt diet showed a trend towards glomerular damage; however, the effects were small and not significant. Similarly, there were few effects of angiotensin II infusion on morphology and functional study on a low-salt diet


CONCLUSIONS
These data clearly show that a high-salt intake increases susceptibility of the kidney to injuries induced by low doses of angiotensin II in normotensive, uni-nephrectomized rats.
Hirawa
N
N
The Department of Nephrology, Asahi Hospital, Yokohama, Japan.
Uehara
Y
Y
Kawabata
Y
Y
Numabe
A
A
Ogawa
N
N
Gomi
T
T
Ikeda
T
T
Goto
A
A
Toyo-oka
T
T
Omata
M
M
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II