Mesenteric arteries responsiveness to acute variations of wall shear stress is impaired in rats with liver cirrhosis

Abstract

Objective. In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis. Materials and Methods. The effect of acute changes in intraluminal flow (0, 10, and 20 μl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 μm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration–response curves to phenylephrine were also obtained. Results. In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME. Conclusions. Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS.

Key Words::

• chromium mesoporphyrin, flow-mediated vasodilation
• indomethacin
• liver cirrhosis
• L-NAME
• splanchnic vasodilation
• wall shear stress

Acknowledgements

We thank Mrs Antonietta Sticca and Dr Sara Montagnese for their expert technical assistance. The research was completely funded by the University of Padova.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.