Cardiovascular autonomic dysfunction, as manifested by impairment of arterial baroreflex, is prevalent irrespective of etiology and contributes to the elevated morbidity and mortality in cirrhotic patients. However, the cellular mechanisms underlying cirrhosis-impaired arterial baroreflex currently remain unknown. In the present study, we examined whether cirrhosis-impaired arterial baroreflex is attributable to the dysfunction of aortic baroreceptor (AB) neurons. In this regard, biliary and nonbiliary cirrhotic rats were generated by 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. As assessed by measuring the heart rate changes during phenylephrine-induced baroreceptor activation, the baroreflex sensitivity was blunted in CBDL and TAA rats. Under the current clamp mode of the patch-clamp technique, the cell excitability was recorded in Di-I labeled AB neurons. The number of action potential discharge in A- and C-type AB neurons was significantly reduced due to increased rheobase and threshold potential in CBDL and TAA rats compared with sham-operated rats. Real-time PCR and western blotting revealed that NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly down-regulated in the nodose ganglion neurons from CBDL and TAA rats compared with sham-operated rats. Consistent with these molecular data, TTX-S NaV currents as well as both TTX-S and TTX-R NaV currents were significantly decreased in A- and C-type AB neurons, respectively, from CBDL and TAA rats compared with sham-operated rats. Taken together, these findings implicate a key cellular mechanism in cirrhosis-impaired arterial baroreflex.
- arterial baroreflex
- aortic baroreceptor neuron
- liver cirrhosis
- voltage-gated sodium channel
- Copyright © 2015, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology