Korean J Nephrol.  2004 Nov;23(6):878-887.

The Effect of Inhibition of Renin-Angiotensin System in Experimental Unilateral Ischemia-Reperfusion Renal Injury

• Lee KW
• Song JH
• Choi DE
• Na KR
• Suh KS
• Shin YT

Abstract

BACKGROUND
It has been suggested that the activation of proinflammatory cytokines and growth factors play an important role in many renal injury processes including ischemia-reperfusion. The activation of renin-angiotensin system in ischemia-reperfusion renal injury may be also involved in injury process. METHODS: In order to evaluate the renal gene expressions of renin, TGF-beta, TNF-alpha, MCP-1, endothelin-1, iNOS, Fas and the role of renin-angiotrensin system (RAS) in experimental unilateral renal ischemia-reperfusion (I-R) injury, 28 male Sprague-Dawley rats weighing 250-270 g underwent sham operation (n=6), I-R injury (clamping left renal artery for 60 minutes) without any treatment (n=11), I-R injury with angiotensin converting enzyme inhibitor (enalapril 100 mg/L in drinking water for one week, n=11) under thiopental sodium anesthesia (50 mg/kg, body weight, I.P.). Systolic blood pressure was measured with tail cuff method before surgery and 24 hours after surgery. Plasma renin activity (PRA) of all study group was measured at the time of sacrifice, 24 hours after surgery. Competitive RT- PCR was performed for the estimation of renin, TGF-beta, TNF-alpha, MCP-1, endothelin-1, iNOS, and Fas gene expression levels of the kidneys. The magnitude of each gene expression was expressed the ratio to beta-actin gene. RESULTS: The systolic blood pressure of untreated I-R injured group (135+/-6 mmHg, mean+/-SE) was significantly higher than those of sham operated (105+/-3 mmHg) rats and enalapril treated I-R injured rats at 24 hour after surgery (98+/-2 mmHg) (p<0.05, p<0.05). PRA of untreated I-R injury group was 6.6+/-1.1 ng/mL/hr and also significantly higher than that of sham operated rats (2.6+/-0.3 ng/mL/hr) (p<0.05). Renal gene expressions of renin, TGF-beta, MCP-1, TNF-alpha, endothelin-1, iNOS and Fas of untreated I-R injured rats were significantly higher than those of sham operated rats at 24 hours after surgery. The level of TGF-beta, TNF-alpha, MCP-1, endothelin-1, iNOS and Fas gene expressions of ACEI treated I-R injured rats was significantly lower than those of untreated I-R injured rats (all, p<0.05). CONCLUSION: With the above result, we speculate that the early up-regulation of renin, TGF-beta, MCP- 1, TNF-alpha, endothelin-1, iNOS, and Fas genes in the kidney may be related to the renal injury mechanism in this model and at least in part, the early activation of renin-angiotensin system of the kidney may be involved in this mechanism.

Keyword

Ischemia-reperfusion; kidney; Renin- angiotensin system; Cytokine; Angiotensin converting enzyme inhibitor

MeSH Terms

Actins
Anesthesia
Animals
Blood Pressure
Body Weight
Cytokines
Drinking Water
Enalapril
Endothelin-1
Gene Expression
Humans
Intercellular Signaling Peptides and Proteins
Kidney
Male
Peptidyl-Dipeptidase A
Plasma
Polymerase Chain Reaction
Rats
Rats, Sprague-Dawley
Renal Artery
Renin
Renin-Angiotensin System*
Tail
Thiopental
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Up-Regulation
Actins
Cytokines
Drinking Water
Enalapril
Endothelin-1
Intercellular Signaling Peptides and Proteins
Peptidyl-Dipeptidase A
Renin
Thiopental
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha