Open AccessChronic angiotensin (1–7) injection accelerates STZ‐induced diabetic renal injury 1
Author(s) -
SHAO Ying,
HE Ming,
ZHOU Li,
YAO Tai,
HUANG Yu,
LU Limin
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00812.x
Subject(s) - medicine , endocrinology , streptozotocin , angiotensin ii receptor type 1 , angiotensin ii , renin–angiotensin system , renal function , diabetes mellitus , kidney , receptor , blood pressure
Aim: The renin‐angiotensin system (RAS) plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. In the past few years, angio‐tensin (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 μg·kg −1 ·h −1 of Ang (1–7) was continually injected through the jugular vein by embedding mini‐osmotic 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‐β1 mRNA levels were measured by real time PCR; ACE, ACE2, and TGF‐β1 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‐β1 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. Conclusion: Exogenous Ang (1–7) injection did not ameliorate STZ‐induced diabetic rat renal injury; on the contrary, it accelerated the progressive diabetic nephropathies.