Dataset Information

Vasomotion of mice mesenteric arteries during low oxygen levels.

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.

SUBMITTER: Westhoff J

PROVIDER: S-EPMC6109325 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

Vasomotion of mice mesenteric arteries during low oxygen levels.

Westhoff J J Weismüller K K Koch C C Mann V V Weigand M A MA Henrich M M

European journal of medical research 20180825 1

<h4>Background</h4>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.<h4>Methods</h4>The present study compared the effects of various degrees of hypoxia on second-order ...[more]

PMID: 30144829

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Project description:Arterial hyperpolarization to acetylcholine (ACh) reflects coactivation of K(Ca)3.1 (IK(Ca)) channels and K(Ca)2.3 (SK(Ca)) channels in the endothelium that transfers through myoendothelial gap junctions and diffusible factor(s) to affect smooth muscle relaxation (endothelium-derived hyperpolarizing factor [EDHF] response). However, ACh can differentially activate K(Ca)3.1 and K(Ca)2.3 channels, and we investigated the mechanisms responsible in rat mesenteric arteries. K(Ca)3.1 channel input to EDHF hyperpolarization was enhanced by reducing external [Ca(2+)](o) but blocked either with forskolin to activate protein kinase A or by limiting smooth muscle [Ca(2+)](i) increases stimulated by phenylephrine depolarization. Imaging [Ca(2+)](i) within the endothelial cell projections forming myoendothelial gap junctions revealed increases in cytoplasmic [Ca(2+)](i) during endothelial stimulation with ACh that were unaffected by simultaneous increases in muscle [Ca(2+)](i) evoked by phenylephrine. If gap junctions were uncoupled, K(Ca)3.1 channels became the predominant input to EDHF hyperpolarization, and relaxation was inhibited with ouabain, implicating a crucial link through Na(+)/K(+)-ATPase. There was no evidence for an equivalent link through K(Ca)2.3 channels nor between these channels and the putative EDHF pathway involving natriuretic peptide receptor-C. Reconstruction of confocal z-stack images from pressurized arteries revealed K(Ca)2.3 immunostain at endothelial cell borders, including endothelial cell projections, whereas K(Ca)3.1 channels and Na(+)/K(+)-ATPase alpha(2)/alpha(3) subunits were highly concentrated in endothelial cell projections and adjacent to myoendothelial gap junctions. Thus, extracellular [Ca(2+)](o) appears to modify K(Ca)3.1 channel activity through a protein kinase A-dependent mechanism independent of changes in endothelial [Ca(2+)](i). The resulting hyperpolarization links to arterial relaxation largely through Na(+)/K(+)-ATPase, possibly reflecting K(+) acting as an EDHF. In contrast, K(Ca)2.3 hyperpolarization appears mainly to affect relaxation through myoendothelial gap junctions. Overall, these data suggest that K(+) and myoendothelial coupling evoke EDHF-mediated relaxation through distinct, definable pathways.

Dataset Information

Vasomotion of mice mesenteric arteries during low oxygen levels.

Background

Methods

Results

Conclusions

Publications

Vasomotion of mice mesenteric arteries during low oxygen levels.

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