Nitric oxide synthase-independent release of nitric oxide induced by KCl in the perfused mesenteric bed of the rat

V. E. Mendizabal, I. Poblete, Alejandro Lomniczi, V. Rettori, J. P. Huidobro-Toro, E. Adler-Graschinsky

Research output: Contribution to journalArticle

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Abstract

The aim of the present study was to test whether the contractile responses elicited by KCl in the rat mesenteric bed are coupled to the release of nitric oxide (NO). Contractions induced by 70 mM KCl were coincident with the release of NO to the perfusate. The in vitro exposure to the nitric oxide synthase (NOS) inhibitor L-N(ω)-nitro-L-arginine methyl ester, L-NAME (1-100 μM) potentiated the vascular responses to 70 mM KCl and, unexpectedly, increased the KCl-stimulated release of NO. Moreover, even after the chronic treatment with L-NAME (70 mg/kg/day during 4 weeks), the KCl-induced release of NO was not reduced, whereas the potentiation of contractile responses was indeed achieved. The possibility that NOS had not been completely inhibited under our experimental conditions can be precluded because NOS activity was significantly inhibited after both L-NAME treatments. After the in vitro treatment with 1 to 100 μM L-NAME, the inhibition of NOS was concentration-dependent (from 50% to 90%). With regard to the basal release of NO, the inhibition caused by L-NAME was not concentration-dependent and reached a maximum of 40%, suggesting that basal NO outflow is only partially dependent on NOS activity. An eventual enhancement of NOS activity caused by KCl was disregarded because the activity of this enzyme measured in homogenates from mesenteric beds perfused with 70 mM KCl was significantly reduced. On the other hand, endothelium removal, employed as a negative control, almost abolished NOS activity, whereas the incubation with the Ca2+ ionophore A23187, employed as a positive control, induced an increase in NOS activity. It is concluded that in the mesenteric arterial bed of the rat, the contractile responses elicited by depolarization through KCl are coincident with a NOS-independent release of NO. This observation, which differs from the results obtained with noradrenaline, do not support the use of KCl as an alternative contractile agent whenever the participation of NO is under study. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)85-91
Number of pages7
JournalEuropean Journal of Pharmacology
Volume409
Issue number1
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

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Nitric Oxide Synthase
Nitric Oxide
NG-Nitroarginine Methyl Ester
Ionophores
Calcimycin
Endothelium
Blood Vessels
Norepinephrine
Enzymes

Keywords

  • Depolarization
  • KCl
  • Mesenteric bed
  • N(ω)-nitro-L-arginine methyl ester
  • Nitric oxide (NO)
  • Nitric oxide (NO) synthase

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Nitric oxide synthase-independent release of nitric oxide induced by KCl in the perfused mesenteric bed of the rat. / Mendizabal, V. E.; Poblete, I.; Lomniczi, Alejandro; Rettori, V.; Huidobro-Toro, J. P.; Adler-Graschinsky, E.

In: European Journal of Pharmacology, Vol. 409, No. 1, 01.12.2000, p. 85-91.

Research output: Contribution to journalArticle

Mendizabal, V. E. ; Poblete, I. ; Lomniczi, Alejandro ; Rettori, V. ; Huidobro-Toro, J. P. ; Adler-Graschinsky, E. / Nitric oxide synthase-independent release of nitric oxide induced by KCl in the perfused mesenteric bed of the rat. In: European Journal of Pharmacology. 2000 ; Vol. 409, No. 1. pp. 85-91.
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T1 - Nitric oxide synthase-independent release of nitric oxide induced by KCl in the perfused mesenteric bed of the rat

AU - Mendizabal, V. E.

AU - Poblete, I.

AU - Lomniczi, Alejandro

AU - Rettori, V.

AU - Huidobro-Toro, J. P.

AU - Adler-Graschinsky, E.

PY - 2000/12/1

Y1 - 2000/12/1

N2 - The aim of the present study was to test whether the contractile responses elicited by KCl in the rat mesenteric bed are coupled to the release of nitric oxide (NO). Contractions induced by 70 mM KCl were coincident with the release of NO to the perfusate. The in vitro exposure to the nitric oxide synthase (NOS) inhibitor L-N(ω)-nitro-L-arginine methyl ester, L-NAME (1-100 μM) potentiated the vascular responses to 70 mM KCl and, unexpectedly, increased the KCl-stimulated release of NO. Moreover, even after the chronic treatment with L-NAME (70 mg/kg/day during 4 weeks), the KCl-induced release of NO was not reduced, whereas the potentiation of contractile responses was indeed achieved. The possibility that NOS had not been completely inhibited under our experimental conditions can be precluded because NOS activity was significantly inhibited after both L-NAME treatments. After the in vitro treatment with 1 to 100 μM L-NAME, the inhibition of NOS was concentration-dependent (from 50% to 90%). With regard to the basal release of NO, the inhibition caused by L-NAME was not concentration-dependent and reached a maximum of 40%, suggesting that basal NO outflow is only partially dependent on NOS activity. An eventual enhancement of NOS activity caused by KCl was disregarded because the activity of this enzyme measured in homogenates from mesenteric beds perfused with 70 mM KCl was significantly reduced. On the other hand, endothelium removal, employed as a negative control, almost abolished NOS activity, whereas the incubation with the Ca2+ ionophore A23187, employed as a positive control, induced an increase in NOS activity. It is concluded that in the mesenteric arterial bed of the rat, the contractile responses elicited by depolarization through KCl are coincident with a NOS-independent release of NO. This observation, which differs from the results obtained with noradrenaline, do not support the use of KCl as an alternative contractile agent whenever the participation of NO is under study. (C) 2000 Elsevier Science B.V.

AB - The aim of the present study was to test whether the contractile responses elicited by KCl in the rat mesenteric bed are coupled to the release of nitric oxide (NO). Contractions induced by 70 mM KCl were coincident with the release of NO to the perfusate. The in vitro exposure to the nitric oxide synthase (NOS) inhibitor L-N(ω)-nitro-L-arginine methyl ester, L-NAME (1-100 μM) potentiated the vascular responses to 70 mM KCl and, unexpectedly, increased the KCl-stimulated release of NO. Moreover, even after the chronic treatment with L-NAME (70 mg/kg/day during 4 weeks), the KCl-induced release of NO was not reduced, whereas the potentiation of contractile responses was indeed achieved. The possibility that NOS had not been completely inhibited under our experimental conditions can be precluded because NOS activity was significantly inhibited after both L-NAME treatments. After the in vitro treatment with 1 to 100 μM L-NAME, the inhibition of NOS was concentration-dependent (from 50% to 90%). With regard to the basal release of NO, the inhibition caused by L-NAME was not concentration-dependent and reached a maximum of 40%, suggesting that basal NO outflow is only partially dependent on NOS activity. An eventual enhancement of NOS activity caused by KCl was disregarded because the activity of this enzyme measured in homogenates from mesenteric beds perfused with 70 mM KCl was significantly reduced. On the other hand, endothelium removal, employed as a negative control, almost abolished NOS activity, whereas the incubation with the Ca2+ ionophore A23187, employed as a positive control, induced an increase in NOS activity. It is concluded that in the mesenteric arterial bed of the rat, the contractile responses elicited by depolarization through KCl are coincident with a NOS-independent release of NO. This observation, which differs from the results obtained with noradrenaline, do not support the use of KCl as an alternative contractile agent whenever the participation of NO is under study. (C) 2000 Elsevier Science B.V.

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