Alteration of endothelin-1 concentration in STZ-induced diabetic rat nephropathy. Effects of a PGI(2) derivative.
BACKGROUND
Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography.


METHODS
We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I(2) derivative to investigate the effect of PGI(2) in diabetic vascular disturbance.


RESULTS
Renal weight, urinary albumin, urinary N-acetyl-beta,D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI(2) derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI(2) derivative is effective in diabetic nephropathy. As the PGI(2) derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels.


CONCLUSIONS
In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI(2) derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI(2) derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.
Itoh
Y
Y
Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Nakai
A
A
Kakizawa
H
H
Makino
M
M
Fujiwara
K
K
Kobayashi
T
T
Kato
T
T
Nagata
M
M
Oda
N
N
Katsumata
H
H
Nagasaka
A
A
Itoh
M
M
D000419:Albuminuria / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D011464:Epoprostenol / Q000494:pharmacology; D005215:Fasting / Q000097:blood; D007004:Hypoglycemic Agents / Q000652:urine; D007668:Kidney / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size; D051381:Rats
D001786:Blood Glucose; D019332:Endothelin-1; D007004:Hypoglycemic Agents; D011464:Epoprostenol