title: Nitric oxide and Kir6.1 potassium channel mediate isoquercitrin-induced endothelium-dependent and independent vasodilation in the mesenteric arterial bed of rats.
abstract: The vascular effect of flavonoid isoquercitrin was investigated in the perfused mesenteric vascular bed of rats. In preparations with functional endothelium isoquercitrin (100, 300 and 1000nmol) dose-dependently reduced the perfusion pressure by 13±2.2, 33±3.9, and 58±3.7mm Hg, respectively. Endothelium removal or inhibition of the nitric oxide synthase enzymes by l-NAME did not change the effects of 100 and 300 nmol isoquercitrin, but reduced by 30-40% the vasodilation induced by 1000 nmol isoquercitrin. Perfusion with nutritive solution containing 40mM KCl abolished the vasodilatory effect of all isoquercitrin doses. Treatment with glibenclamide, a Kir6.1 (ATP-sensitive) potassium channel blocker, inhibited vasodilation induced by 100 and 300 nmol isoquercitrin, but only partially reduced the effect of 1000 nmol isoquercitrin. The non-selective KCa (calcium-activated) potassium channel blocker tetraethylammonium, but not the selective KCa1.1 channel blocker iberiotoxin, reduced by around 60% vasodilation induced by all isoquercitrin doses. In addition, association of tetraethylammonium and glibenclamide, or l-NAME and glibenclamide, fully inhibited isoquercitrin-induced vasodilation. Our study shows that isoquercitrin induces vasodilation in resistance arteries, an effect mediated by K(+) channel opening and endothelial nitric oxide production.
authors: Laboratory of Electrophysiology and Cardiovascular Pharmacology, Faculty of Health Sciences, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, km 12, P.O. Box 533, 79 804-970 Dourados, MS, Brazil. Electronic address: arquimedesgasparotto@gmail.com.
authors: Arquimedes
authors: A
authors: Gasparotto Junior
authors: Laboratory of Cardiovascular Biology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors: Renê
authors: R
authors: Dos Reis Piornedo
authors: Laboratory of Cardiovascular Biology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors: Jamil
authors: J
authors: Assreuy
authors: Laboratory of Cardiovascular Biology, Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: j.e.silva.santos@ufsc.br.
authors: José Eduardo
authors: JE
authors: Da Silva-Santos
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D054086:KATP Channels / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D054086:KATP Channels; C092520:uK-ATP-1 potassium channel; C016527:isoquercitrin; D009569:Nitric Oxide; D011794:Quercetin
keywords: Acetylcholine chloride (Pubchem CID 6060); Glibenclamide (PubChem CID: 3488); Iberiotoxin (PubChem CID 16132435); Indomethacin (PubChem CID 3715); Isoquercitrin; Isoquercitrin (PubChem CID 5280804); Mesenteric arterial bed; N-Nitroarginine methyl ester (PubChem CID 39836); Phenylephrine hydrochloride (PubChem CID: 5284443); Potassium channel; Tetraethylammonium chloride (PubChem CID 5946); Vasodilation