A Novel Role for HNO in Local and Spreading Vasodilatation in Rat Mesenteric Resistance Arteries

作者：Yuill Kathryn H; Yarova Polina; Kemp Harper Barbara K; Garland Christopher J; Dora Kim A^*

来源：Antioxidants and Redox Signaling, 2011, 14(9): 1625-1635.

DOI：10.1089/ars.2010.3279

Nitric oxide-mediated vasodilatation has previously been attributed to the uncharged form of the molecule (NO(center dot)), but increasing evidence suggests that nitroxyl (HNO) may play a significant role in endothelium-dependent relaxation. The aim of this study was to investigate the mechanisms underlying HNO-mediated vasodilatation in phenylephrine pre-constricted pressurized (70mmHg) mesenteric arteries, and on membrane currents in isolated smooth muscle cells using whole cell and perforated patch clamp recordings. Angeli's salt (AS: nitroxyl donor), evoked concentration-dependent vasodilatation that was insensitive to the NO(center dot) scavengers carboxy-PTIO and hydroxocobalamin (HXC), but sensitive to either the HNO scavenger L-cysteine, K-channel blockers (4-AP and iberiotoxin), raised [K(+)](o), or inhibition of soluble guanylyl cyclase (ODQ). AS-evoked smooth muscle hyperpolarization significantly augmented K(V) current in an ODQ sensitive manner, and also increased the BK(Ca) current. Importantly, 30 mu M AS initiated conducted or spreading vasodilatation, and following blockade of endothelial K-channels (TRAM-34 and apamin), ACh was able to evoke similar L-cysteine-sensitive conducted dilatation. These data show that vasodilatation induced by HNO is mediated by both K(V) and BK(Ca) channels, and suggest a physiological role in vasodilatation through the vasculature. Antioxid. Redox Signal. 14, 1625-1635.

• 出版日期2011-5