Abstract: PO0166
DPP-4 Inhibitor Attenuated Renal Vasoconstriction Following Ischemia-Reperfusion Injury in Cirrhotic Rats
Session Information
- AKI Mechanisms - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Chuang, Chiao-Lin, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
- Huang, Hui-Chun, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
Background
Cirrhotic patients may develop esophageal varices to cope with portal hypertension. Variceal bleeding is usually associated with hypotension and ischemia-reperfusion injury (IRI) which may activate endogenous vasoconstrictors, leading to severe renal vasoconstriction and renal failure (so called hepatorenal syndrome).
Previous studies reported that dipeptidyl peptidase-4 inhibitor (DPP4i) could attenuate the endothelin-1 (ET-1) induced vasocontraction and increase vasodilation. The aim of this study is to delineate the effect of DPP4i in renal vascular reactivity of cirrhotic rats following IRI.
Methods
Male S-D rats were used for experiments. Biliary cirrhosis was created by common bile duct ligation (CBDL). Control group received sham surgery (SHAM). After surgery, Linagliptin (3 mg/kg/d) or distilled water (DW) was administered for 28 days. On the 29th day, bilateral renal pedicles were clamped with microvascular clamps for 45 minutes in IRI group. The clamps were then removed followed with 60 minutes of reperfusion. Kidneys were perfused in situ via right renal artery for continuous monitoring of renal perfusion pressure.
Results
There was no difference in mean arterial pressure, heart rate, portal pressure, and blood sugar between DW and DPP4i treated rats. IRI enhanced renal vascular response to ET-1 in both SHAM (p=0.027) and CBDL (p=0.025) rats, implying renal vasoconstriction. Compared with corresponding DW-treated rats, DPP4i treatment abrogated renal hyperreactivity following IRI in CBDL rats (p=0.036), but not in SHAM rats (p=0.737).
Conclusion
We concluded that DPP4i may attenuate the development of renal vasoconstriction following IRI in cirrhotic rats. The potentially mechanisms remained to be elucidated.
Concentration-response curves to ET-1 in perfused kidneys of SHAM (A) and BDL (B) rats.