A novel role for HNO in local and spreading vasodilatation in rat mesenteric resistance arteries

Kathryn H Yuill, Polina Yarova, B K Kemp-Harper, C J Garland, K A Dora

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24 Citations (Scopus)

Abstract

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 BKCa 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 BKCa channels, and suggest a physiological role in vasodilatation through the vasculature.
Original languageEnglish
Pages (from-to)1625-1635
Number of pages11
JournalAntioxidants & Redox Signaling
Volume14
Issue number9
DOIs
Publication statusPublished - May 2011

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