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Tani, Takao

doi:10.1254/fpj.77.221

Cited by 8 publications

(1 citation statement)

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“…Because FA is toxic in cultured endothelial cells (inhibition of mitosis, increased apoptosis), vascular smooth muscle cells and cardiomyocytes (Conklin et al, 1998), it is, thus, speculated that endogenously generated FA induces endothelium dysfunction by which it accelerates diabetic complications such as atherosclerosis (Deng and Yu, 1999). However, FA induces a concentration-dependent relaxation in isolated blood vessels (Tani, 1981; Conklin et al, 2004; Zhang et al, 2018) yet the relevance of this effect in vascular physiology is unclear.…”

Section: Introductionmentioning

confidence: 99%

Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia

et al. 2019

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Formaldehyde (FA), the smallest aldehyde, is generated endogenously, and is widespread in the environment in foods, beverages and as a gas phase product of incomplete combustion. The main metabolite of FA, formate, was increased significantly in murine urine (∼3×) after overnight feeding. Because feeding increases mesenteric blood flow, we explored the direct effects of FA in isolated murine superior mesenteric artery (SMA). Over the concentration range of 30–1,200 μM, FA strongly and reversibly relaxed contractions of SMA induced by three different agonists: phenylephrine (PE), thromboxane A 2 analog (U46,619) and high potassium (60K, 60 mM K + ). Formate (to 1.5 mM) induced a modest relaxation. FA (>1,500 μM) irreversibly depressed vascular function in SMA indicating vasotoxicity. The sensitivity (EC 50 ) but not the efficacy (% relaxation) of FA-induced relaxations was dependent on blood vessel type (SMA << aorta) and contractile agonist (PE, EC 50 = 52 ± 14 μM; U46,619, EC 50 = 514 ± 129 μM; 60K, EC 50 = 1,093 ± 87 μM). The most sensitive component of FA vasorelaxation was within physiological levels (30–150 μM) and was inhibited significantly by: (1) mechanically impaired endothelium; (2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); (3) transient receptor potential ankyrin-1 (TRPA1) antagonist (A967079); (4) guanylyl cyclase (GC) inhibitor (ODQ); and, (5) K + channel inhibitor (BaCl 2 ). A similar mechanism of SMA vasorelaxation was stimulated by the TRPA1 agonist cinnamaldehyde. Positive TRPA1 immunofluorescent staining and gene-specific sequence were present in SMA but not in aorta. These data indicate FA, but not formate, robustly relaxes SMA via a sensitive TRPA1- and endothelium-dependent mechanism that is absent in aorta. Thus, as FA levels increase with feeding, FA likely contributes to the physiological reflex of post-prandial hyperemia via SMA vasodilatation.

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Section: Introductionmentioning

confidence: 99%

Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia

et al. 2019

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Formaldehyde regulates vascular tensions through nitric oxide-cGMP signaling pathway and ion channels

et al. 2018

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Vasodilatory effect of formaldehyde via the NO/cGMP pathway and the regulation of expression of KATP, BKCa and L-type Ca2+ channels

Zhao

et al. 2019

Toxicology Letters

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Formaldehyde (FA), a well-known toxic gas molecule similar to nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H 2 S), is widely produced endogenously via numerous biochemical pathways, and has a number of physiological roles in the biosystem. We attempted to investigate the vasorelaxant effects of FA and their underlying mechanisms. We found that FA induced vasorelaxant effects on rat aortic rings in a concentration-dependent manner. The NO/ cyclic guanosine 5′ monophosphate (cGMP) pathway was up-regulated when the rat aortas were treated with FA. The expression of large-conductance Ca 2+ -activated K + (BK Ca ) channel subunits α and β of the rat aortas was increased by FA. Similarly, the levels of ATP-sensitive K + (K ATP ) channel subunits K ir 6.1 and K ir 6.2 were also up-regulated when the rat aortas were incubated with FA. In contrast, levels of the L-type Ca 2+ channel (LTCC) subunits, Ca v 1.2 and Ca v 1.3, decreased dramatically with increasing concentrations of FA. We demonstrated that the regulation of FA on vascular contractility may be via the up-regulation of the NO/cGMP pathway and the modulation of ion channels, including the upregulated expression of the K ATP and BK Ca channels and the inhibited expression of LTCCs. Further study is needed to explore the in-depth mechanisms of FA induced vasorelaxation.

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Cited by 8 publications

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Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia

Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia

Formaldehyde regulates vascular tensions through nitric oxide-cGMP signaling pathway and ion channels

Vasodilatory effect of formaldehyde via the NO/cGMP pathway and the regulation of expression of KATP, BKCa and L-type Ca2+ channels

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