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

摘要: Formaldehyde (FA), the smallest aldehyde, is generated endogenously, and widespread in environment foods, beverages as a gas phase product of incomplete combustion. The main metabolite FA, formate, was increased significantly murine urine (3x) after overnight feeding. Because feeding increases mesenteric blood flow, we explored direct effects FA isolated superior artery (SMA). Over concentration range 30-1,200 μM, strongly reversibly relaxed contractions SMA induced by three different agonists: phenylephrine (PE), thromboxane A2 analog (U46,619) high potassium (60K, 60 mM K+). Formate (to 1.5 mM) modest relaxation. (>1,500 μM) irreversibly depressed vascular function indicating vasotoxicity. sensitivity (EC50) but not efficacy (% relaxation) FA-induced relaxations dependent on vessel type (SMA << aorta) contractile agonist (PE, EC50=52±14 μM; U46,619, EC50=514±129 60K, EC50=1,093±87 μM). most sensitive component vasorelaxation within physiological levels (30-150 inhibited 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 (BaCl2). A similar mechanism stimulated TRPA1 cinnamaldehyde. Positive immunofluorescent staining gene-specific sequence were present aorta. These data indicate robustly relaxes via TRPA1- endothelium-dependent that absent Thus, increase with feeding, likely contributes to reflex post-prandial hyperemia vasodilatation.