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Gene Transfer.jpgExercise training enhances NOS-1 (neuronal isoform) expression in sympathetic (1) and parasympathetic intra cardiac ganglia (2). Physical training also accelerates vagally mediated recovery of heart rate following exertion (3) and increases in vagal tone (4). These effects are believed to result from reduced sympathetic (1) and increased parasympathetic control (2) of heart rate, and are likely due to enhanced NO bioavailability. We are using adenovirus-mediated NOS-1 gene transfer into right atrial tissue to mimic these effects and investigate this hypothesis. 

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2. Danson EJF, Mohan RM, Garland T, Paterson DJ. NO-cGMP pathway enhances the heart rate response to peripheral vagal nerve stimulation in exercise trained mice. (2001) Circulation 104:S833

3. Sugawara J, Murakami H, Maeda S, Kuno S, Matsuda M. Change in post-exercise vagal reactivation with exercise training and detraining in young men. (2001) Eur J Appl Physiol 85:259-263.

4. Yamamoto K, Miyachi M, Saitoh T, Yoshioka A, Onodera S. Effects of endurance training on resting and post-exercise cardiac autonomic control.(2001) Med Sci Sports Exerc 33:1496-1502

5. Mohan, R.M.M., *Golding, S., Heaton, D.A., Danson, E.J.F. & Paterson, D.J. (2004). Targeting neuronal nitric oxide synthase with gene transfer to modulate cardiac autonomic function. Prog. Biophys. Mol. Biol. 84:321-344 [Full text] *equal contribution

6. Danson, E.J., Mankia, K.S., Golding, S., Dawson,T., Everatt, L., Cai, S.J., Channon, K.M. & Paterson, D.J. (2004) Impaired regulation of neuronal NOS and heart rate during exercise in mice lacking one nNOS allele. J Physiol.558(3):963-974  [ Full Text]

7.Heaton, D.A., Golding, S., Bradley, C.P., Dawson, T.A., Cai, S., Channon, K.M. & Paterson, D.J. (2005) Targeted nNOS gene transfer into the cardiac vagus rapidly increases parasympathetic function in the pig. J. Mol. Cell. Cardiol.39(1):159-64 [Abstract/Full Text]

8. Wang, L., Li, D., Plested, C.P., Dawson, T.D., Teschemacher, A. and Paterson, D.J. (2006) Noradrenrgic neuron-specific overexpression of nNOS in cardiac sympathetic nerves decreases neurotransmission. J Mol Cell Cardiol.Aug;41(2):364-70 [Abstract/Full Text]

9.  Heaton, D.A., Lei, M., Li, D., Golding, S., Dawson, T.A., Mohan, R.M., and Paterson, D.J. (2006) Remodelling of Cardiac Pacemaker I_CaL and Beta-adrenergic Responsiveness in Hypertension following nNOS Gene Transfer. Hypertension 48:443-452 [Abstract/Full Text].

10. Heaton, D.A., Li, D., Almond, S.C., Dawson, T.A., Wang, L., Channon, K.M., and Paterson, D.J. (2007) Gene Transfer of nNOS into Intracardiac Ganglia Reverses Vagal Impairment in Hypertensive Rats Hypertension 49:380-388[Abstract/Full Text]

11. Li, D., Wang, L., Chee-Wan, L., Dawson, T.A., and Paterson, D.J. (2007) Noradrenergic Cell Specific Gene Transfer With Neuronal Nitric Oxide Synthase Reduces Cardiac Sympathetic Neurotransmission in Hypertensive Rats. Hypertension 50(1):69-74 [Abstract/Full Text].

12. Wang, L., Henrich, M., Buckler, K., McMenamin, M., Mee, C.J., Sattelle, D.B., and Paterson, D.J. (2007) Neuronal nitric oxide synthase gene transfer decreases [Ca2+]i in cardiac sympathetic neurons J Mol Cell Cardiol. 43(6):717-25[Abstract/Full Text]

13. Dawson, T.A., Li, D., Woodward, T.D., Barber, Z.E., Wang, L. and Paterson, D.J. (2008) Cardiac Cholinergic NO-cGMP Signalling Following Acute Myocardial Infarction and nNOS Gene Transfer Am. J. Physiol. Heart Circ. Physiol.295(3):H990-H998 [Abstract/Full Text]

14. Bursill, C.A., McNeill, E., Wang, L., Hibbert, O.C., Wade-Martins, R., Paterson, D.J., Greaves, D.R. and Channon, K.M. (2009) Lentiviral gene transfer to reduce atherosclerosis progression by long-term CC-chemokine inhibition. Gene Ther. 16(1):93-102 [Abstract/Full Text]

15. Danson, E.J., Li, D., Wang, L., Dawson, T.A. and Paterson, D.J. (2009) Targeting cardiac sympathovagal imbalance using gene transfer of nitric oxide synthase. J. Mol. Cell Cardiol. 46(4):482-9 [Abstract/Full Text]

16. Li D, Nikiforova, N., Lu, C-J. Wannop, K., McMenamin, M., Lee CW, Buckler K, Paterson DJ. (2013). Targeted neuronal nitric oxide synthase transgene delivery into stellate neurons reverses impaired intracellular calcium transients in prehypertensive rats. Hypertension Jan;61(1):202-207 [Abstract/Full Text].

17. Li, D, Lu, C-J, Hao, G., Wright, H. Woodward, L, Liu, K., Vergari, E., Surdo, N.C., Herring, N., Zaccolo, M., & Paterson, D.J. (2015). Efficacy of B type natriuretic peptide is coupled to phosphodiesterase 2A in cardiac sympathetic neurons. Hypertension 2015 Jul;66(1):190-8 [Abstract/Full Text] [Editorial]

18. Lu C-J, Hao, G. Nikiforova, N. Larsen, H.E., Liu, K., Cabtree, M.J., Li, D., Herring, H., & Paterson, D.J. (2015)  Capon modulates neuronal calcium handling and cardiac sympathetic neurotransmission during dysautonomia in hypertension.  Hypertension. 65(6):1288-97. PMID: 25916729 [Full text]