Chronic angiotensin (1-7) injection accelerates STZ-induced diabetic renal injury.
OBJECTIVE
The renin-angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angiotensin (Ang) (1-7) has been reported to counteract the effects of Ang II and was even considered as a new therapeutical target in RAS. The present study aimed to investigate the effect of Ang (1-7) administration on a diabetic animal model and the modulation on local RAS.


METHODS
Streptozotocin (STZ) injection-induced diabetic rats were used in the experiment. The animals were divided into 3 groups: (1) control; (2) STZ-induced diabetes; and (3) STZ-induced diabetes with chronic Ang (1-7) treatment [D+Ang(1-7)]. In the D+Ang(1-7) group, a dose of 25 microg x kg(-1) x h(-1) of Ang (1-7) was continually injected through the jugular vein by embedding miniosmotic pump for 6 weeks. Plasma glucose, ratio of kidney to body weight, and 24 h urine protein and serum creatinine were monitored by conventional measurement. Plasma and renal Ang II levels were measured by radioimmunoassay. Ang-converting enzyme (ACE), ACE2, Ang II type 1 (AT1) receptor, Ang II type 2 (AT2) receptor, Ang (1-7) Mas receptor, and TGF- beta1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF- beta1 protein levels were analyzed by Western blotting.


RESULTS
The renal function of diabetic rats was significantly retrogressed when compared with that of control rats. After the treatment by constant Ang (1-7) vein injection for 6 weeks, renal function was found to be even worse than diabetic rats, and both TGF-beta1 mRNA and protein levels were elevated in the D+Ang(1-7) group compared with the diabetic rats. The real-time PCR result also showed an increase in ACE mRNA expression and decrease in ACE2 mRNA level in the D+Ang(1-7) group when compared with diabetic rats. The number of AT1 receptors increased in the Ang (1-7)-injected group, while the number of AT2 and Mas receptors decreased.


CONCLUSIONS
Exogenous Ang (1-7) injection did not ameliorate STZinduced diabetic rat renal injury; on the contrary, it accelerated the progressive diabetic nephropathies.
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Ying
Y
Shao
Ming
M
He
Li
L
Zhou
Tai
T
Yao
Yu
Y
Huang
Li-min
LM
Lu
D000803:Angiotensin I / Q000633:toxicity*; D000818:Animals; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D008297:Male; D010446:Peptide Fragments / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018076:DNA, Complementary; D010446:Peptide Fragments; D012313:RNA; D000803:Angiotensin I; C118790:angiotensin I (1-7)