Impaired nitric oxide- and endothelium-derived hyperpolarizing factor-dependent dilation of renal afferent arteriole in Dahl salt-sensitive rats

Yuri Ozawa, Koichi Hayashi, Takeshi Kanda, Koichiro Honma, Ichiro Takamatsu, Satoru Tatematsu, Kyoko Yoshioka, Hiroo Kumagai, Shu Wakino, Takao Saruta

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Backgrounds and Aims: We previously demonstrated that acetylcholine elicited nitric oxide dependent sustained and endothelium-derived hyperpolarizing factor (EDHF)-dependent transient dilation of afferent arterioles. The present study examined whether free radicals interacted with nitric oxide-dependent and EDHF-dependent vasodilator mechanisms in renal microvessels of salt-sensitive hypertension, using the isolated perfused hydronephrotic kidney. Methods and Results: Following the pretreatment with indomethacin (100 μmol/L) with or without nitro-L-arginine methylester (100 μmol/L), the effect of acetylcholine on noradrenaline (0.3 μmol/L)-induced constriction was evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although acetylcholine (0.01-10 μmol/L) caused dose-dependent and sustained vasodilation of afferent arterioles, attenuated dilation was observed in Dahl salt-sensitive rats, compared with that in salt-resistant rats (58 ± 4 vs 101 ± 11% reversal at 10 μmol/L acetylcholine). In the presence of nitro-L-arginine methylester, acetylcholine elicited only transient dilation, with vasodilator response blunted in Dahl salt-sensitive rats (64 ± 4 vs 100 ± 9% reversal at 10 μmol/L acetylcholine). Furthermore, chronic (8-10 weeks) treatment with tempol caused partial restoration of acetylcholine (10 μmol/L)-induced sustained arteriolar dilation (71 ± 3% reversal), but complete reversal of transient dilation (92 ± 4% reversal). Finally, acute treatment with tempol not only improved the sustained component of the acetylcholine-induced dilation but also restored the impaired responsiveness of transient dilation in Dahl salt-sensitive rats. Conclusion: Both sustained (nitric oxide-mediated) and transient (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to enhanced free radical activity. A reversal of the sustained and transient vasodilation by the acute tempol treatment suggests possible interaction between free radicals and EDHF as well as increased bioavailability of nitric oxide.

Original languageEnglish
Pages (from-to)272-277
Number of pages6
JournalNephrology
Volume9
Issue number5
DOIs
Publication statusPublished - 2004 Oct

Fingerprint

Inbred Dahl Rats
Arterioles
Acetylcholine
Dilatation
Nitric Oxide
Kidney
Salts
Free Radicals
Endothelium
Vasodilator Agents
Vasodilation
Arginine
Microvessels
Constriction
Indomethacin
Biological Availability
Norepinephrine
Hypertension

Keywords

  • Acetylcholine
  • Afferent arteriole
  • Endothelium-derived hyperpolarizing factor
  • Hypertension
  • Nitric oxide

ASJC Scopus subject areas

  • Nephrology

Cite this

Impaired nitric oxide- and endothelium-derived hyperpolarizing factor-dependent dilation of renal afferent arteriole in Dahl salt-sensitive rats. / Ozawa, Yuri; Hayashi, Koichi; Kanda, Takeshi; Honma, Koichiro; Takamatsu, Ichiro; Tatematsu, Satoru; Yoshioka, Kyoko; Kumagai, Hiroo; Wakino, Shu; Saruta, Takao.

In: Nephrology, Vol. 9, No. 5, 10.2004, p. 272-277.

Research output: Contribution to journalArticle

Ozawa, Yuri ; Hayashi, Koichi ; Kanda, Takeshi ; Honma, Koichiro ; Takamatsu, Ichiro ; Tatematsu, Satoru ; Yoshioka, Kyoko ; Kumagai, Hiroo ; Wakino, Shu ; Saruta, Takao. / Impaired nitric oxide- and endothelium-derived hyperpolarizing factor-dependent dilation of renal afferent arteriole in Dahl salt-sensitive rats. In: Nephrology. 2004 ; Vol. 9, No. 5. pp. 272-277.
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abstract = "Backgrounds and Aims: We previously demonstrated that acetylcholine elicited nitric oxide dependent sustained and endothelium-derived hyperpolarizing factor (EDHF)-dependent transient dilation of afferent arterioles. The present study examined whether free radicals interacted with nitric oxide-dependent and EDHF-dependent vasodilator mechanisms in renal microvessels of salt-sensitive hypertension, using the isolated perfused hydronephrotic kidney. Methods and Results: Following the pretreatment with indomethacin (100 μmol/L) with or without nitro-L-arginine methylester (100 μmol/L), the effect of acetylcholine on noradrenaline (0.3 μmol/L)-induced constriction was evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although acetylcholine (0.01-10 μmol/L) caused dose-dependent and sustained vasodilation of afferent arterioles, attenuated dilation was observed in Dahl salt-sensitive rats, compared with that in salt-resistant rats (58 ± 4 vs 101 ± 11{\%} reversal at 10 μmol/L acetylcholine). In the presence of nitro-L-arginine methylester, acetylcholine elicited only transient dilation, with vasodilator response blunted in Dahl salt-sensitive rats (64 ± 4 vs 100 ± 9{\%} reversal at 10 μmol/L acetylcholine). Furthermore, chronic (8-10 weeks) treatment with tempol caused partial restoration of acetylcholine (10 μmol/L)-induced sustained arteriolar dilation (71 ± 3{\%} reversal), but complete reversal of transient dilation (92 ± 4{\%} reversal). Finally, acute treatment with tempol not only improved the sustained component of the acetylcholine-induced dilation but also restored the impaired responsiveness of transient dilation in Dahl salt-sensitive rats. Conclusion: Both sustained (nitric oxide-mediated) and transient (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to enhanced free radical activity. A reversal of the sustained and transient vasodilation by the acute tempol treatment suggests possible interaction between free radicals and EDHF as well as increased bioavailability of nitric oxide.",
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AU - Ozawa, Yuri

AU - Hayashi, Koichi

AU - Kanda, Takeshi

AU - Honma, Koichiro

AU - Takamatsu, Ichiro

AU - Tatematsu, Satoru

AU - Yoshioka, Kyoko

AU - Kumagai, Hiroo

AU - Wakino, Shu

AU - Saruta, Takao

PY - 2004/10

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N2 - Backgrounds and Aims: We previously demonstrated that acetylcholine elicited nitric oxide dependent sustained and endothelium-derived hyperpolarizing factor (EDHF)-dependent transient dilation of afferent arterioles. The present study examined whether free radicals interacted with nitric oxide-dependent and EDHF-dependent vasodilator mechanisms in renal microvessels of salt-sensitive hypertension, using the isolated perfused hydronephrotic kidney. Methods and Results: Following the pretreatment with indomethacin (100 μmol/L) with or without nitro-L-arginine methylester (100 μmol/L), the effect of acetylcholine on noradrenaline (0.3 μmol/L)-induced constriction was evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although acetylcholine (0.01-10 μmol/L) caused dose-dependent and sustained vasodilation of afferent arterioles, attenuated dilation was observed in Dahl salt-sensitive rats, compared with that in salt-resistant rats (58 ± 4 vs 101 ± 11% reversal at 10 μmol/L acetylcholine). In the presence of nitro-L-arginine methylester, acetylcholine elicited only transient dilation, with vasodilator response blunted in Dahl salt-sensitive rats (64 ± 4 vs 100 ± 9% reversal at 10 μmol/L acetylcholine). Furthermore, chronic (8-10 weeks) treatment with tempol caused partial restoration of acetylcholine (10 μmol/L)-induced sustained arteriolar dilation (71 ± 3% reversal), but complete reversal of transient dilation (92 ± 4% reversal). Finally, acute treatment with tempol not only improved the sustained component of the acetylcholine-induced dilation but also restored the impaired responsiveness of transient dilation in Dahl salt-sensitive rats. Conclusion: Both sustained (nitric oxide-mediated) and transient (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to enhanced free radical activity. A reversal of the sustained and transient vasodilation by the acute tempol treatment suggests possible interaction between free radicals and EDHF as well as increased bioavailability of nitric oxide.

AB - Backgrounds and Aims: We previously demonstrated that acetylcholine elicited nitric oxide dependent sustained and endothelium-derived hyperpolarizing factor (EDHF)-dependent transient dilation of afferent arterioles. The present study examined whether free radicals interacted with nitric oxide-dependent and EDHF-dependent vasodilator mechanisms in renal microvessels of salt-sensitive hypertension, using the isolated perfused hydronephrotic kidney. Methods and Results: Following the pretreatment with indomethacin (100 μmol/L) with or without nitro-L-arginine methylester (100 μmol/L), the effect of acetylcholine on noradrenaline (0.3 μmol/L)-induced constriction was evaluated in kidneys from Dahl salt-sensitive and salt-resistant rats. Although acetylcholine (0.01-10 μmol/L) caused dose-dependent and sustained vasodilation of afferent arterioles, attenuated dilation was observed in Dahl salt-sensitive rats, compared with that in salt-resistant rats (58 ± 4 vs 101 ± 11% reversal at 10 μmol/L acetylcholine). In the presence of nitro-L-arginine methylester, acetylcholine elicited only transient dilation, with vasodilator response blunted in Dahl salt-sensitive rats (64 ± 4 vs 100 ± 9% reversal at 10 μmol/L acetylcholine). Furthermore, chronic (8-10 weeks) treatment with tempol caused partial restoration of acetylcholine (10 μmol/L)-induced sustained arteriolar dilation (71 ± 3% reversal), but complete reversal of transient dilation (92 ± 4% reversal). Finally, acute treatment with tempol not only improved the sustained component of the acetylcholine-induced dilation but also restored the impaired responsiveness of transient dilation in Dahl salt-sensitive rats. Conclusion: Both sustained (nitric oxide-mediated) and transient (EDHF-mediated) components of acetylcholine-induced afferent arteriolar dilation were attenuated in Dahl salt-sensitive rats, which was attributed, in part, to enhanced free radical activity. A reversal of the sustained and transient vasodilation by the acute tempol treatment suggests possible interaction between free radicals and EDHF as well as increased bioavailability of nitric oxide.

KW - Acetylcholine

KW - Afferent arteriole

KW - Endothelium-derived hyperpolarizing factor

KW - Hypertension

KW - Nitric oxide

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