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  • Open Access

The nitroxyl anion (NO): a novel regulator of sGC and vascular tone

BMC Pharmacology20055 (Suppl 1) :S20

  • Published:


  • Nitric Oxide
  • Glibenclamide
  • KATP Channel
  • Channel Inhibitor
  • Methoxamine


Traditionally the vascular effects of nitric oxide (NO) have been attributed to the free radical form of NO (NO) yet the reduced form of NO (NO-) is also produced endogenously and vasodilates both large conduit and small resistance-like arteries. Interestingly, NO and NO- have been shown to have distinct mechanisms of action in the cardiovascular system, particularly in the heart. This study aimed to determine if the vasorelaxant effects of NO- differed to those of NO in rat small mesenteric resistance arteries.

Materials and Methods

Mesenteric arteries (~350 μm diameter) were obtained from male Sprague-Dawley rats, mounted in small vessel myographs and isometric force and intracellular membrane potential measured simultaneously. Vessels were precontracted to ~50% of maximum (determined by K+(124 mM)) with methoxamine. Cumulative concentration-response curves to NO (NO gas), the NO- donor, Angeli's salt and the NO-independent soluble guanylate cyclase (sGC) activator, YC-1 were examined.


Vasorelaxation to Angeli's salt (pEC50 = 7.02 ± 0.67 -log M; Rmax = 96.0 ± 2.2%, n = 4) was accompanied by simultaneous vascular smooth muscle cell hyperpolarisation (pEC50 = 6.82 ± 0.32, 10 μM AS -17.8 ± 4.4 mV, n = 4). In contrast, maximal vasorelaxation to NO (pEC50 = 6.82 ± 0.39, 92.1 ± 1.3%) was achieved before a small hyperpolarization response was observed at 1 μM NO (-4.9 ± 2.3 mV, n = 5). Both relaxation and hyperpolarisation responses to Angeli's salt were significantly attenuated (P < 0.05, n = 5) by the NO- scavenger, L-cysteine (3 mM) and abolished by the sGC inhibitor, ODQ (10 μM; P < 0.05, n = 4). The Kv channel inhibitor, 4-aminopyridine (1 mM) caused a 4-fold (P < 0.05, n = 4) decrease in sensitivity to Angeli's salt and abolished the hyperpolarisation response (P < 0.05). In contrast glibenclamide (KATP channel inhibitor) and charybdotoxin (BKCa/IKCa channel inhibitor) were without effect. YC-1 also induced vasorelaxation and hyperpolarisation in rat small mesenteric arteries.


In conclusion, in rat small mesenteric arteries, NO- mediates relaxation in part via cGMP-dependent activation of Kv channels. In contrast, NO-mediated vasorelaxation occurs independently of vascular smooth muscle hyperpolarisation. Thus, the redox siblings NO and NO- have distinct mechanisms of vasorelaxation in resistance-like arteries.

Authors’ Affiliations

Department of Pharmacology, Monash University, Clayton, VIC, 3800, Australia


© BioMed Central Ltd 2005