Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats

Juan Gao, Hao Zhang, Khang D. Le, Jie Chao, Lie Gao

Research output: Contribution to journalArticle

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Abstract

Background We have previously documented the finding that central angiotensin type 2 receptors (AT2R) negatively modulate sympathetic outflow and arterial blood pressure (BP). In this study, we investigated the effects of intracerebroventricular (icv) infusion of Compound 21 (C21), the first selective nonpeptide AT2R agonist, on norepinephrine (NE) excretion and BP in rats. Methods C21 was infused icv for 7 days, using a micro-osmotic pump. Urinary NE concentration was measured using the NE enzyme immunoassay kit. BP was recorded by radiotelemetry. After 7 days, the rats were killed and three relevant samples from sympathetic brain regions and the cerebral cortex were obtained by micro-punching to measure neuronal nitric oxide synthase (nNOS) protein expression by western blot. In addition, the influence of C21 on neuronal potassium current (IKv) was determined by whole-cell patch-clamp in a neuron cell line, CATH.a. Results (i) Icv treatment with C21 significantly decreased both the concentration and the amount of NE in night time urine, but had no effect on daytime urine. (ii) C21-treated rats exhibited a slight but significant decrease in BP. (iii) The effects of C21 on NE excretion and BP were abolished by use of the AT2R antagonist, PD123319, and nitric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME). (iv) C21 treatment significantly upregulated nNOS expression in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM), but not in the nucleus of the solitary tract (NTS) and cerebral cortex. (v) In CATH.a neurons, C21 treatment significantly increased IKv, and this increase was completely abolished by PD123319 and L-NAME. Conclusions These Results demonstrate a central inhibitory influence of C21 on sympathetic outflow by means of a nNOS-dependent mechanism that might be mediated by facilitating the neuronal potassium channel.

Original languageEnglish (US)
Pages (from-to)724-730
Number of pages7
JournalAmerican Journal of Hypertension
Volume24
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Angiotensin Type 2 Receptor
Norepinephrine
Nitric Oxide Synthase Type I
Blood Pressure
NG-Nitroarginine Methyl Ester
Cerebral Cortex
Angiotensin II Type 2 Receptor Blockers
Urine
Intraventricular Infusions
Neurons
Solitary Nucleus
Paraventricular Hypothalamic Nucleus
Potassium Channels
Immunoenzyme Techniques
Nitric Oxide Synthase
Hypothalamus
Potassium
Arterial Pressure
Therapeutics
Western Blotting

Keywords

  • angiotensin type 2 receptor
  • blood pressure
  • central nervous system
  • hypertension; norepinephrine
  • potassium current

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats. / Gao, Juan; Zhang, Hao; Le, Khang D.; Chao, Jie; Gao, Lie.

In: American Journal of Hypertension, Vol. 24, No. 6, 01.06.2011, p. 724-730.

Research output: Contribution to journalArticle

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T1 - Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats

AU - Gao, Juan

AU - Zhang, Hao

AU - Le, Khang D.

AU - Chao, Jie

AU - Gao, Lie

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Background We have previously documented the finding that central angiotensin type 2 receptors (AT2R) negatively modulate sympathetic outflow and arterial blood pressure (BP). In this study, we investigated the effects of intracerebroventricular (icv) infusion of Compound 21 (C21), the first selective nonpeptide AT2R agonist, on norepinephrine (NE) excretion and BP in rats. Methods C21 was infused icv for 7 days, using a micro-osmotic pump. Urinary NE concentration was measured using the NE enzyme immunoassay kit. BP was recorded by radiotelemetry. After 7 days, the rats were killed and three relevant samples from sympathetic brain regions and the cerebral cortex were obtained by micro-punching to measure neuronal nitric oxide synthase (nNOS) protein expression by western blot. In addition, the influence of C21 on neuronal potassium current (IKv) was determined by whole-cell patch-clamp in a neuron cell line, CATH.a. Results (i) Icv treatment with C21 significantly decreased both the concentration and the amount of NE in night time urine, but had no effect on daytime urine. (ii) C21-treated rats exhibited a slight but significant decrease in BP. (iii) The effects of C21 on NE excretion and BP were abolished by use of the AT2R antagonist, PD123319, and nitric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME). (iv) C21 treatment significantly upregulated nNOS expression in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM), but not in the nucleus of the solitary tract (NTS) and cerebral cortex. (v) In CATH.a neurons, C21 treatment significantly increased IKv, and this increase was completely abolished by PD123319 and L-NAME. Conclusions These Results demonstrate a central inhibitory influence of C21 on sympathetic outflow by means of a nNOS-dependent mechanism that might be mediated by facilitating the neuronal potassium channel.

AB - Background We have previously documented the finding that central angiotensin type 2 receptors (AT2R) negatively modulate sympathetic outflow and arterial blood pressure (BP). In this study, we investigated the effects of intracerebroventricular (icv) infusion of Compound 21 (C21), the first selective nonpeptide AT2R agonist, on norepinephrine (NE) excretion and BP in rats. Methods C21 was infused icv for 7 days, using a micro-osmotic pump. Urinary NE concentration was measured using the NE enzyme immunoassay kit. BP was recorded by radiotelemetry. After 7 days, the rats were killed and three relevant samples from sympathetic brain regions and the cerebral cortex were obtained by micro-punching to measure neuronal nitric oxide synthase (nNOS) protein expression by western blot. In addition, the influence of C21 on neuronal potassium current (IKv) was determined by whole-cell patch-clamp in a neuron cell line, CATH.a. Results (i) Icv treatment with C21 significantly decreased both the concentration and the amount of NE in night time urine, but had no effect on daytime urine. (ii) C21-treated rats exhibited a slight but significant decrease in BP. (iii) The effects of C21 on NE excretion and BP were abolished by use of the AT2R antagonist, PD123319, and nitric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME). (iv) C21 treatment significantly upregulated nNOS expression in the paraventricular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM), but not in the nucleus of the solitary tract (NTS) and cerebral cortex. (v) In CATH.a neurons, C21 treatment significantly increased IKv, and this increase was completely abolished by PD123319 and L-NAME. Conclusions These Results demonstrate a central inhibitory influence of C21 on sympathetic outflow by means of a nNOS-dependent mechanism that might be mediated by facilitating the neuronal potassium channel.

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KW - blood pressure

KW - central nervous system

KW - hypertension; norepinephrine

KW - potassium current

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