Vasomotion of mice mesenteric arteries during low oxygen levels

Abstract

Abstract Background Ischemia of intestinal organs is a main cause of complications in surgical intensive care patients. Changes in the tonus of arteries contributing to vascular resistance play an important role in the determination of blood flow and thus oxygen supply of various abdominal organs. It is generally acknowledged that hypoxia itself is able to alter arterial tonus and thus blood flow. Methods The present study compared the effects of various degrees of hypoxia on second-order mesenteric arteries from male C57BL/6J mice. After vessel isolation and preparation, we assessed vessel diameter using an arteriograph perfusion chamber. Investigating mechanisms promoting hypoxia-induced vasodilatation, we performed experiments in Ca2+-containing and Ca2+-free solutions, and furthermore, Ca2+-influx was inhibited by NiCl2, eNOS−/−-, and TASK1−/−-mice were investigated too. Results Mild hypoxia 14.4% O2 induced, in 50% of mesenteric artery segments from wild-type (wt) mice, a vasodilatation; severe hypoxia recruited further segments responding with vasodilatation reaching 80% under anoxia. However, the extension of dilatation of luminal arterial diameter reduced from 1.96% ± 0.55 at 14.4% O2 to 0.68% ± 0.13 under anoxia. Arteries exposed to hypoxia in Ca2+-free solution responded to lower oxygen levels with increasing degree of vasodilatation (0.85% ± 0.19 at 14.4% O2 vs. 1.53% ± 0.42 at 2.7% O2). Inhibition of voltage-gated Ca2+-influx using NiCl2 completely diminished hypoxia-induced vasodilatation. Instead, all arterial segments investigated constricted. Furthermore, we did not observe altered hypoxia-induced vasomotion in eNOS−/−- or TASK1−/− mice compared to wt animals. Conclusions The present study demonstrated that hypoxic vasodilatation in mice mesenteric arteries is mediated by a NO-independent mechanism. In this experimental setting, we found evidence for Ca2+-mediated activation of ion channels causing hypoxic vasodilatation.

Keywords

• Vasomotion
• Hypoxia
• Mesenteric artery
• Mice