A functional coupling between carbon monoxide and nitric oxide contributes to increased vasopressin neuronal activity in heart failure rats

Wagner L. Reis, Vinicia C. Biancardi, Yiqiang Zhou, Javier E. Stern

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Despite the pathophysiological importance of neurohumoral activation in patients with heart failure (HF), the precise underlying mechanisms contributing to elevated vasopressin (VP) activation in HF remains unknown. Carbon monoxide (CO) is a gaseous neurotransmitter in the central nervous system that stimulates VP neuronal firing activity. Recently, we showed that the excitatory effect of CO on VP neurons in the hypothalamic paraventricular nucleus (PVN) was mediated by inhibition of nitric oxide (NO). Given that previous studies showed that VP neuronal activity is enhanced, whereas NO inhibitory signaling is blunted in HF rats, we tested whether an enhanced endogenous CO availability within the PVN contributes to elevated VP neuronal activity and blunted NO signaling in HF rats. We found that both haeme-oxygenase 1 (the CO-synthesizing enzyme) protein andmRNAexpression levels were enhanced in thePVNof HF compared with sham rats (18% and 38%, respectively). We report that in sham rats, bath application of a CO donor (tricarbonyldichlororuthenium dimer) increased the firing activity of identified PVN VP neurons (P < 05), whereas inhibition of endogenous CO production (Tin-protoporphyrin IX [SnPP]) failed to affect neuronal activity. In HF rats, however, SnPP decreased VP activity (P < 05), an effect that was occluded by previous NO synathase blockade NG-nitro-larginine methyl ester. Finally, we found that SnPP increased the mean frequency of -aminobutyric acid inhibitory postsynaptic currents in VP neurons in HF (P < 05) but not sham rats. Our results support an enhanced endogenous CO excitatory signaling in VP neurons, which likely contributes to blunted NO and -aminobutyric acid inhibitory function in HF rats.

Original languageEnglish (US)
Pages (from-to)2052-2066
Number of pages15
Issue number5
Publication statusPublished - May 2016


ASJC Scopus subject areas

  • Endocrinology

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