The impaired vasodilatation in rat renal interlobar arteries after hypoxia/re‐oxygenation is endothelium independent

Abstract

Renal vasculature plays an important role in renal ischemia/reperfusion injury. We showed recently that hypoxia/re‐oxygenation combined with low dose norepinephrine treatment increases the angiotensin II responses in interlobar arteries. Since angiotensin II activates constrictor and dilator systems we hypothesized an impaired vasodilatation in this context.To test the hypothesis rat interlobar arteries were studied by using wire myography. The dilatory capacity was investigated by application of acetylcholine (10‐9 to 10‐5 mol/l). Hypoxia (95% N2, 5% CO2 for 60 min) alone followed by re‐oxygenation (95% O2, 5% CO2, 10 min) did not affect vasodilatation. However, norepinephrine in a non‐constrictor dose (10‐9 mol/l) applied during hypoxia resulted in a decreased response to acetylcholine. The contribution of the nitric oxide system, COX‐products, and endothelial derived hyperpolarizing factor to reduced dilatation was tested by pretreatment with L‐NAME (10‐4 mol/l), indomethacin (10‐5 mol/l), TRAM‐34 (10‐6 mol/), and UCL1684 (10‐7 mol/l), respectively. L‐NAME decreased the acetylcholine response after hypoxia/re‐oxygenation stronger compared to control conditions, while indomethacin, TRAM‐34, and UCL1684 did not affect it. Endothelium‐independent effects were analyzed by using the NO‐donor SNP and simultaneous blocking of endothelium‐dependent NO production. SNP significantly reduces vasodilation after hypoxia+norepinephrine/re‐oxygenation (H+NE/R). Passive stiffness of arteries was not altered in our experimental setup.H+NE/R provokes an impairment of the dilatory response to acetylcholine in renal arteries. Our data suggest that the endothelial nitric oxide system, COX products, or TRAM‐34 and UCL1684 inhibitable potassium channels do not contribute to reduced dilatation. The results indicate changed dilatory signaling pathways in vascular smooth muscle cells.Support or Funding InformationThis study was financially supported by a grant of the German Research Council to A.P and P.B.P (FG 1368, DFG PA 479/10‐1 and PA 479/10‐2).