Decreased excitability and voltage-gated sodium currents in aortic baroreceptor neurons contribute to the impairment of arterial baroreflex in cirrhotic rats

Choong Ku Lee, Kwang Hwa Park, Soon Koo Baik, Seong Woo Jeong

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Abstract

Cardiovascular autonomic dysfunction, which is manifested by an impairment of the arterial baroreflex, is prevalent irrespective of etiology and contributes to the increased morbidity and mortality in cirrhotic patients. However, the cellular mechanisms that underlie the cirrhosisimpaired arterial baroreflex remain unknown. In the present study, we examined whether the cirrhosis-impaired arterial baroreflex is attributable to the dysfunction of aortic baroreceptor (AB) neurons. Biliary and nonbiliary cirrhotic rats were generated via common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Histological and molecular biological examinations confirmed the development of fibrosis in the livers of both cirrhotic rat models. The heart rate changes during phenylephrineinduced baroreceptor activation indicated that baroreflex sensitivity was blunted in the CBDL and TAA rats. Under the current-clamp mode of the patch-clamp technique, cell excitability was recorded in DiI-labeled AB neurons. The number of action potential discharges in the A-and C-type AB neurons was significantly decreased because of the increased rheobase and threshold potential in the CBDL and TAA rats compared with sham-operated rats. Real-time PCR and Western blotting indicated that the NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly downregulated in the nodose ganglion neurons from the CBDL and TAA rats compared with the shamoperated rats. Consistent with these molecular data, the tetrodotoxinsensitive NaV currents and the tetrodotoxin-resistant NaV currents were significantly decreased in A-and C-type AB neurons, respectively, from the CBDL and TAA rats compared with the shamoperated rats. Taken together, these findings implicate a key cellular mechanism in the cirrhosis-impaired arterial baroreflex.

Original languageEnglish
Pages (from-to)R1088-R1101
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume310
Issue number11
DOIs
Publication statusPublished - 2016 Jun

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Pressoreceptors
Baroreflex
Thioacetamide
Sodium
Neurons
Common Bile Duct
Ligation
Fibrosis
Nodose Ganglion
Tetrodotoxin
Patch-Clamp Techniques
Intraperitoneal Injections
Liver Cirrhosis
Action Potentials
Real-Time Polymerase Chain Reaction
Down-Regulation
Heart Rate
Western Blotting
Morbidity
Mortality

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

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title = "Decreased excitability and voltage-gated sodium currents in aortic baroreceptor neurons contribute to the impairment of arterial baroreflex in cirrhotic rats",
abstract = "Cardiovascular autonomic dysfunction, which is manifested by an impairment of the arterial baroreflex, is prevalent irrespective of etiology and contributes to the increased morbidity and mortality in cirrhotic patients. However, the cellular mechanisms that underlie the cirrhosisimpaired arterial baroreflex remain unknown. In the present study, we examined whether the cirrhosis-impaired arterial baroreflex is attributable to the dysfunction of aortic baroreceptor (AB) neurons. Biliary and nonbiliary cirrhotic rats were generated via common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Histological and molecular biological examinations confirmed the development of fibrosis in the livers of both cirrhotic rat models. The heart rate changes during phenylephrineinduced baroreceptor activation indicated that baroreflex sensitivity was blunted in the CBDL and TAA rats. Under the current-clamp mode of the patch-clamp technique, cell excitability was recorded in DiI-labeled AB neurons. The number of action potential discharges in the A-and C-type AB neurons was significantly decreased because of the increased rheobase and threshold potential in the CBDL and TAA rats compared with sham-operated rats. Real-time PCR and Western blotting indicated that the NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly downregulated in the nodose ganglion neurons from the CBDL and TAA rats compared with the shamoperated rats. Consistent with these molecular data, the tetrodotoxinsensitive NaV currents and the tetrodotoxin-resistant NaV currents were significantly decreased in A-and C-type AB neurons, respectively, from the CBDL and TAA rats compared with the shamoperated rats. Taken together, these findings implicate a key cellular mechanism in the cirrhosis-impaired arterial baroreflex.",
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T1 - Decreased excitability and voltage-gated sodium currents in aortic baroreceptor neurons contribute to the impairment of arterial baroreflex in cirrhotic rats

AU - Lee, Choong Ku

AU - Park, Kwang Hwa

AU - Baik, Soon Koo

AU - Jeong, Seong Woo

PY - 2016/6

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N2 - Cardiovascular autonomic dysfunction, which is manifested by an impairment of the arterial baroreflex, is prevalent irrespective of etiology and contributes to the increased morbidity and mortality in cirrhotic patients. However, the cellular mechanisms that underlie the cirrhosisimpaired arterial baroreflex remain unknown. In the present study, we examined whether the cirrhosis-impaired arterial baroreflex is attributable to the dysfunction of aortic baroreceptor (AB) neurons. Biliary and nonbiliary cirrhotic rats were generated via common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Histological and molecular biological examinations confirmed the development of fibrosis in the livers of both cirrhotic rat models. The heart rate changes during phenylephrineinduced baroreceptor activation indicated that baroreflex sensitivity was blunted in the CBDL and TAA rats. Under the current-clamp mode of the patch-clamp technique, cell excitability was recorded in DiI-labeled AB neurons. The number of action potential discharges in the A-and C-type AB neurons was significantly decreased because of the increased rheobase and threshold potential in the CBDL and TAA rats compared with sham-operated rats. Real-time PCR and Western blotting indicated that the NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly downregulated in the nodose ganglion neurons from the CBDL and TAA rats compared with the shamoperated rats. Consistent with these molecular data, the tetrodotoxinsensitive NaV currents and the tetrodotoxin-resistant NaV currents were significantly decreased in A-and C-type AB neurons, respectively, from the CBDL and TAA rats compared with the shamoperated rats. Taken together, these findings implicate a key cellular mechanism in the cirrhosis-impaired arterial baroreflex.

AB - Cardiovascular autonomic dysfunction, which is manifested by an impairment of the arterial baroreflex, is prevalent irrespective of etiology and contributes to the increased morbidity and mortality in cirrhotic patients. However, the cellular mechanisms that underlie the cirrhosisimpaired arterial baroreflex remain unknown. In the present study, we examined whether the cirrhosis-impaired arterial baroreflex is attributable to the dysfunction of aortic baroreceptor (AB) neurons. Biliary and nonbiliary cirrhotic rats were generated via common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Histological and molecular biological examinations confirmed the development of fibrosis in the livers of both cirrhotic rat models. The heart rate changes during phenylephrineinduced baroreceptor activation indicated that baroreflex sensitivity was blunted in the CBDL and TAA rats. Under the current-clamp mode of the patch-clamp technique, cell excitability was recorded in DiI-labeled AB neurons. The number of action potential discharges in the A-and C-type AB neurons was significantly decreased because of the increased rheobase and threshold potential in the CBDL and TAA rats compared with sham-operated rats. Real-time PCR and Western blotting indicated that the NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly downregulated in the nodose ganglion neurons from the CBDL and TAA rats compared with the shamoperated rats. Consistent with these molecular data, the tetrodotoxinsensitive NaV currents and the tetrodotoxin-resistant NaV currents were significantly decreased in A-and C-type AB neurons, respectively, from the CBDL and TAA rats compared with the shamoperated rats. Taken together, these findings implicate a key cellular mechanism in the cirrhosis-impaired arterial baroreflex.

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