ArticleHypertension (Dallas, Tex. : 1979)2022
Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension.
Article in Hypertension (Dallas, Tex. : 1979), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Healthy cardiac myocytes can decrease sympathetic hyperexcitability in the early stages of hypertension.Frontiers in synaptic neuroscience · 2022Article
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundDisruption of cyclic nucleotide signaling in sympathetic postganglionic neurons contributes to impaired intracellular calcium handling (Ca
methodsUsing a combination of single-cell RNA sequencing together with Forster resonance energy transfer-based sensors to monitor cyclic adenosine 3',5'-monophosphate, PKA (protein kinase A)-dependent phosphorylation and cGMP (cyclic guanosine 3',5'-monophosphate), we tested the hypothesis that dysregulation occurs in a sub-family of PDEs in the cytosol and outer mitochondrial membrane of neurons from the stellate ganglion.
resultsPDE2A, 6D, 7A, 9A genes were highly expressed in young Wistar neurons and also conserved in neurons from spontaneously hypertensive rats (SHRs). In stellate neurons from prehypertensive SHRs, we found the levels of cyclic adenosine 3',5'-monophosphate and cGMP at the outer mitochondrial membrane were decreased compared with normal neurons. The reduced cyclic adenosine 3',5'-monophosphate response was due to the hydrolytic activity of overexpressed PDE2A2 located at the mitochondria. Normal cyclic adenosine 3',5'-monophosphate levels were re-established by inhibition of PDE2A. There was also a greater PKA-dependent phosphorylation in the cytosol and at the outer mitochondrial membrane in spontaneously hypertensive rat neurons, where this response was regulated by protein phosphatases. The cGMP response was only restored by inhibition of PDE6.
conclusionsWhen taken together, these results suggest that site-specific inhibition of PDE2A and PDE6D at the outer mitochondrial membrane may provide a therapeutic target to ameliorate cardiac sympathetic impairment during the onset of hypertension.
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