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A cellular mechanism underlying impairment of arterial baroreflex in rats with portal hypertension

      Portal hypertension is a frequent clinical syndrome that is characterized by an increased portal venous pressure, and is most commonly caused by chronic liver disease. Clinical studies have suggested that portal hypertension causes cardiovascular autonomic dysfunction including impairment of arterial baroreflex. In the present study, we examined whether portal hypertension causes impairment of arterial baroreflex and functional plasticity of the aortic baroreceptor (AB) neurons. In this regard, we produced portal hypertensive (PH) rats by a partial ligation of the portal vein. One week after surgery, the portal venous pressure was significantly increased in PH rats compared with sham-operated rats. As assessed by measuring the heart rate changes during phenylephrine-induced baroreceptor activation, the baroreflex sensitivity was blunted in PH rats. Under the current clamp mode of the patch-clamp technique, the cell excitability was recorded in Di-I labeled AB neurons. The frequency of action potential discharge in A- and C-type AB neurons was significantly reduced due to increased rheobase and threshold potential in PH rats compared with sham-operated rats. Real-time PCR and western blotting experiments revealed that NaV1.7, NaV1.8, and NaV1.9 transcripts and proteins were significantly down-regulated in the nodose ganglion neurons from PH rats compared with sham-operated rats. Consistent with these molecular data, TTX-sensitive NaV currents as well as both TTX-sensitive and TTX-resistant NaV currents were significantly decreased in A- and C-type AB neurons, respectively, from PH rats compared with sham-operated rats. Taken together, these data suggest that portal hypertension blunts arterial baroreflex through attenuating excitability of the AB neurons. The ionic mechanisms underlying the hypoexcitability may include down-regulation of voltage-gated sodium channels. This research was supported by Basic Science research Program through the National Research Foundation (NRF) funded by the Ministry of Education, Science and Technology (2013R1A1A2013424).
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