The prevalence of cardiac and renal failure has been rising rapidly over the last decade. Despite this, there are no effective treatments for cardiac or renal failure. The concomitant existence of both cardiac and renal disease is termed the cardiorenal syndrome. The primary interest in my laboratory is to investigate the mechanisms underlying the pathogenesis of cardiorenal syndrome and to develop novel treatments for this disease state. To this end, our recent data indicate that reduced nitric oxide bioavailability and resulting inflammation contribute to the development of renal disease in heart failure. Accordingly, we are currently investigating novel therapeutic approaches which can restore nitric oxide bioavailability in cardiorenal syndrome.

  • Development of novel treatment approaches for cardiorenal syndrome
  • The role of the microbiome in cardiorenal syndrome
  • Exploring factors that influence nitric oxide production: Role of the L-arginine transporters

1. Beverly Giam, Sanjaya Kuruppu, Po-Yin Chu, Francine Marquez, April Fielder, Duncan Horlock, Helen Kiriazis, Xiao-Jun Du, David M. Kaye and Niwanthi W. Rajapakse. N-acetylcysteine attenuates the development of renal fibrosis in transgenic mice with dilated cardiomyopathy.

Sci Rep. (In press).

2. Marques FZ, Nelson EM, Chu PY, Horlock D, Fiedler A, Ziemann M, Tan JK, Kuruppu S, Rajapakse NW, El-Osta A, Mackay CR, Kaye DM. High Fibre Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in DOCA-Salt Hypertensive Mice.  Circulation. 2016 Mar 7;135(10):964-977.    

3. Rajapakse NW, Kuruppu S, Smith AI. Letter by Rajapakse et al Regarding Article “Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition”. Circulation.  134:e9-e10. 2016.

4. Rajapakse NW, Head GA, Kaye DM. Say NO to obesity related hypertension: Role of the L-arginine-Nitric Oxide Pathway. Hypertension. 67; 813-9. 2016.                       

5. Kuruppu S, Rajapakse NW, Spicer AJ, Parkington HC, Smith AI. Stimulating the activity of amyloid-beta degrading enzymes: A novel approach for the therapeutic manipulation of amyloid beta levels. J Alzheimers Dis. 54; 891-5; 2016.

6. Giam B, Kuruppu S, Head GA, Kaye DM, Rajapakse NW. Effects of dietary L-arginine on nitric oxide bioavailability in obese normotensive and obese hypertensive subjects. Nutrients. 8; pii: E362, 2016.

7. Giam B, Chu P-Y, Kuruppu S, Smith AI, Horlock D, Kiriazis H, Du X-J, Kaye DM, Rajapakse NW. N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure. Physiological Reports. 4; pii:e12757; 2016.

8. Smith AI, Rajapakse NW, Kleifeld O, Lomonte B, Sikanyika NL, Spicer AJ, Hodgson WC, Conroy PJ, Small DH, Kaye DM, Parkington HC, Whisstock JC, Kuruppu S. N-terminal domain of Bothrops asper Myotoxin II Enhances the Activity of Endothelin Converting Enzyme-1 and Neprilysin. Sci Rep. 6; 22413, 2016.                              

9. Rajapakse NW, Karim F, Evans RG, Kaye DM, Head GA. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice. PLoS One. 2015 Jul 17;10(7):e0131424.  

10. Rajapakse NW, Nanayakkara S, Kaye DM. Pathogenesis and treatment of the cardiorenal syndrome: Implications of L-arginine-nitric oxide pathway impairment. Pharmacol Ther. 2015 May 16. pii: S0163-7258(15)00102-3. Invited Review.                               

11. Rajapakse NW, Johnston T, Kiriazis H, Chin-Dusting JP, Du XJ, Kaye DM. Augmented endothelial l-arginine transport ameliorates pressure-overload-induced cardiac hypertrophy. Exp Physiol. 2015 Jul 1;100(7):796-804.                                          

12. Kuruppu S, Rajapakse NW, Dunstan RA, Smith AI. Nitric oxide inhibits the production of soluble endothelin converting enzyme-1. Mol Cell Biochem. 2014 Nov;396(1-2):49-54.

13. Rajapakse NW, Karim F, Straznicky NE, Fernandez S, Evans RG, Head GA, Kaye DM.Augmented endothelial-specific L-arginine transport prevents obesity-induced hypertension. Acta Physiol (Oxf). 2014 Sep;212(1):39-48.     

14. Konstantinidis G, Head GA, Evans RG, Nguyen-Huu TP, Venardos K, Croft KD, Mori TA, Kaye DM, Rajapakse NW. Endothelial cationic amino acid transporter-1 overexpression can prevent oxidative stress and increases in arterial pressure in response to superoxide dismutase inhibition in mice. Acta Physiol (Oxf). 2014 Apr;210(4):845-53.    

15. Rajapakse NW, Chong AL, Zhang WZ, Kaye DM. Insulin-mediated activation of the L-arginine nitric oxide pathway in man, and its impairment in diabetes. PLoS One. 2013 May 2;8(5):e61840.                                                                                                      

16. Kuruppu S, Rajapakse NW, Smith AI Endothelin-converting enzyme-1 inhibition and renoprotection in end-stage renal disease. Pflugers Arch. 2013 Jul;465(7):929-34. Review.                                   

17. Rajapakse NW, Mattson DL. Role of cellular L-arginine uptake and nitric oxide production on renal blood flow and arterial pressure regulation.  Curr Opin Nephrol Hypertens. 2013 Jan;22(1):45-50. Review.               

18. Rajapakse NW, Kuruppu S, Hanchapola I, Venardos K, Mattson DL, Smith AI, Kaye DM, Evans RG. Evidence that renal arginine transport is impaired in spontaneously hypertensive rats. Am J Physiol Renal Physiol. 2012 Jun 15;302(12):F1554-62.                      

19. Rajapakse NW, and Mattson DL. Role of L-arginine uptake mechanisms in renal blood flow responses to angiotensin II in rats. Acta Physiologica. 203:391-400: 2011.                        

20. Rajapakse, NW, De Miguel C., Das S., and Mattson D. 2008. Exogenous L-arginine ameliorates angiotensin II-induced hypertension and renal damage. Hypertension. 52(6):1084-90, 2008.

(Featured on the cover page of Hypertension).


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