title: Cyclic nucleotide regulation of cardiac sympatho-vagal responsiveness.
abstract: Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are now recognized as important intracellular signalling molecules that modulate cardiac sympatho-vagal balance in the progression of heart disease. Recent studies have identified that a significant component of autonomic dysfunction associated with several cardiovascular pathologies resides at the end organ, and is coupled to impairment of cyclic nucleotide targeted pathways linked to abnormal intracellular calcium handling and cardiac neurotransmission. Emerging evidence also suggests that cyclic nucleotide coupled phosphodiesterases (PDEs) play a key role limiting the hydrolysis of cAMP and cGMP in disease, and as a consequence this influences the action of the nucleotide on its downstream biological target. In this review, we illustrate the action of nitric oxide-CAPON signalling and brain natriuretic peptide on cGMP and cAMP regulation of cardiac sympatho-vagal transmission in hypertension and ischaemic heart disease. Moreover, we address how PDE2A is now emerging as a major target that affects the efficacy of soluble/particulate guanylate cyclase coupling to cGMP in cardiac dysautonomia.
authors.affiliation: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Paterson
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D010727:Phosphoric Diester Hydrolases / Q000502:physiology; D054969:Primary Dysautonomias / Q000503:physiopathology
chemical_list: D009569:Nitric Oxide; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D006152:Cyclic GMP