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

Kathryn H Yuill, Polina Yarova, Barbara Kathryn Kemp-Harper, Christopher J Garland, Kim Dora

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)


Nitric oxide mediated vasodilatation has previously been attributed to the uncharged form of the molecule (NO*), 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 (70 mmHg) 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* 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 KV current in an ODQ sensitive manner, and also increased the BKCa current. Importantly, 30 microM 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 KV and BKCa channels, and suggest a physiological role in vasodilatation through the vasculature.
Original languageEnglish
Pages (from-to)1625 - 1635
Number of pages10
JournalAntioxidants and Redox Signaling
Publication statusPublished - 2011

Cite this