Vasoactivity of nitrite in the iliac artery of the toad Rhinella marina

Am J Physiol Regul Integr Comp Physiol. 2018 Feb 1;314(2):R242-R251. doi: 10.1152/ajpregu.00315.2016. Epub 2017 Nov 14.

Abstract

Nitrite ([Formula: see text]) causes vasodilation in mammals due to the formation of (nitric oxide) NO by endogenous [Formula: see text] reduction in the vascular wall. In this study, we determined if a similar mechanism operates in amphibians. Dual-wire myography of the iliac artery from Rhinella marina showed that applied [Formula: see text] caused a concentration-dependent vasodilation in normoxia (21% O2; EC50: 438 µM). Hypoxia (0.63% O2) significantly increased the maximal dilation to [Formula: see text] by 5% ( P = 0.0398). The addition of oxyhemoglobin significantly increased the EC50 ( P = 0.0144; EC50: 2,236 µM) but did not affect the maximal vasodilation. In contrast, partially deoxygenated hemoglobin (90% desaturation) did not affect the EC50 ( P = 0.1189) but significantly ( P = 0.0012) increased the maximal dilation to [Formula: see text] by 11%. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) completely abolished the response to [Formula: see text] ( P < 0.0001), and of the nitric oxide synthase inhibitors, only N5-(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO; P = 0.0028) significantly reduced the [Formula: see text] vasodilation. The xanthine oxidoreductase inhibitor allopurinol ( P = 0.927), the nitric oxide-scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (C-PTIO; P = 0.478), and disruption of the endothelium ( P = 0.094) did not affect the [Formula: see text] vasodilation. Incubation of iliac arteries with 1 mM [Formula: see text] did not a cause a change in the cGMP concentration (P = 0.407). Plasma [Formula: see text] was found to be 0.86 ± 0.20 µmol/l, while nitrate ([Formula: see text]) was 19.55 ± 2.55 µmol/l. Both cygb and ngb mRNAs were expressed in the iliac artery, and it is possible that these globins facilitate [Formula: see text] reduction in hypoxia. In addition, [Formula: see text] intracellular disproportionation processes could be important in the generation of NO from [Formula: see text].

Keywords: amphibian; nitric oxide; nitrite; nitrite reductase; vascular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphibian Proteins / genetics
  • Amphibian Proteins / metabolism
  • Animals
  • Bufo marinus
  • Cytoglobin / genetics
  • Cytoglobin / metabolism
  • Female
  • Hemoglobins / metabolism
  • Iliac Artery / drug effects*
  • Iliac Artery / metabolism
  • In Vitro Techniques
  • Male
  • Neuroglobin / genetics
  • Neuroglobin / metabolism
  • Nitric Oxide / metabolism
  • Nitrite Reductases / metabolism
  • Oxidation-Reduction
  • Oxyhemoglobins / metabolism
  • Sodium Nitrite / metabolism
  • Sodium Nitrite / pharmacology*
  • Vasodilation / drug effects*
  • Vasodilator Agents / metabolism
  • Vasodilator Agents / pharmacology*

Substances

  • Amphibian Proteins
  • Cytoglobin
  • Hemoglobins
  • Neuroglobin
  • Oxyhemoglobins
  • Vasodilator Agents
  • Nitric Oxide
  • deoxyhemoglobin
  • Nitrite Reductases
  • Sodium Nitrite