Aims: 

Nitric oxide occurs in several redox forms, including NO^• and NO^-, which can each contribute to endothelium-dependent relaxation. Here we studied the contribution of potassium channels in local and conducted dilatation in resistance arteries to NO^-.

Methods: 

Arterial diameter recordings were obtained from small mesenteric arteries pressurized to 70 mm Hg. Arterial tone was generated with phenylephrine or high potassium (45 mM).

Results: 

Angeli's salt (NO^- donor) in concentrations 100 nM - 100 mM caused complete local dilatation, similar to the effect of NO^•-gassed solutions. The free radical scavenger, carboxy-PTIO, did not alter the dilatation, but addition of the NO^- scavenger L-cysteine markedly inhibited the response. 4-AP (150 mM) and TEA (1 mM) or iberiotoxin (100 nM) attenuated relaxation to Angeli's salt and their combination had an additive effect. The co-application of ODQ (10 mM) further inhibited the local dilatation. High potassium largely inhibited and addition of ODQ completely blocked the local dilatation. In triple-cannulated mesenteric arteries, Angeli's salt also evoked conducted dilatation that propagated more than 2 mm upstream and was suppressed by TEA, 4-AP, high potassium, L-cysteine or endothelial removal. In order to unmask the eNOS-dependent pathway, endothelium-derived hyperpolarization was blocked by SK_Ca and IK_Ca channels inhibitors apamin (50 nM) and TRAM-34 (1 mM). Application of ACh (10 mM) evoked a robust dilatation of the local site, which was accompanied by a conducted vasodilatation. Carboxy-PTIO reduced the local dilatation, but did not affect the conducted response, whilst L-cysteine reduced local and abolished conducted dilatation. Inhibition of eNOS with L-NAME blocked the response.

Conclusions: 

This study suggests that apart from NO^•, the endothelium can also endogenously produce NO^- in amounts sufficient to evoke conducted dilatation. This dilatation was enabled by guanylyl cyclase-mediated opening of K_V and BK_Ca channels; the endothelium was essential for the conducted response, seemingly by providing a pathway for the hyperpolarization produced by K⁺ channels.