NO and endogenous angiotensin II interact in the generation of renal sympathetic nerve activity in conscious rats

Donogh F. McKeogh, Theresa L. O'Donaughy, Virginia Brooks

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high- (HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with L-NAME (10 mg/kg iv) resulted in a profound decline in RSNA, to 42 ± 11% of control (P <0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. L-NAME also caused bradycardia, from 432 ± 23 to 372 ± 11 beats/min postinfusion (P <0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after L-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number4 55-4
DOIs
StatePublished - 2004

Fingerprint

Angiotensin II
Nitric Oxide
Kidney
Nitric Oxide Synthase
NG-Nitroarginine Methyl Ester
Sodium
Heart Rate
Sodium-Restricted Diet
Hydralazine
Angiotensin Receptor Antagonists
Bradycardia
Arterial Pressure

Keywords

  • Heart rate
  • Nitric oxide synthase
  • Sympathetic tone

ASJC Scopus subject areas

  • Physiology

Cite this

NO and endogenous angiotensin II interact in the generation of renal sympathetic nerve activity in conscious rats. / McKeogh, Donogh F.; O'Donaughy, Theresa L.; Brooks, Virginia.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 4 55-4, 2004.

Research output: Contribution to journalArticle

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abstract = "Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high- (HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with L-NAME (10 mg/kg iv) resulted in a profound decline in RSNA, to 42 ± 11{\%} of control (P <0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. L-NAME also caused bradycardia, from 432 ± 23 to 372 ± 11 beats/min postinfusion (P <0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after L-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.",
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N2 - Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high- (HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with L-NAME (10 mg/kg iv) resulted in a profound decline in RSNA, to 42 ± 11% of control (P <0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. L-NAME also caused bradycardia, from 432 ± 23 to 372 ± 11 beats/min postinfusion (P <0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after L-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.

AB - Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high- (HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with L-NAME (10 mg/kg iv) resulted in a profound decline in RSNA, to 42 ± 11% of control (P <0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. L-NAME also caused bradycardia, from 432 ± 23 to 372 ± 11 beats/min postinfusion (P <0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after L-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.

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