Published online before print August 12, 2002, doi: 10.1161/01.CIR.0000027586.64231.1B
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:1275.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Effect of Hyperhomocysteinemia on Plasma or Tissue Adenosine Levels and Renal Function
From the Departments of Physiology and Pharmacology Toxicology, Medical College of Wisconsin, Milwaukee, Wis.
Correspondence to Ai-Ping Zou, MD, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail azou{at}post.its.mcw.edu
Background— Hyperhomocysteinemia (hHcys) is considered an independent risk factor of cardiovascular diseases. Recent studies in our laboratory have shown that hHcys produced glomerular dysfunction and sclerosis independently of hypertension. However, the mechanism mediating these pathogenic effects of homocysteine (Hcys) is poorly understood. Because Hcys and adenosine (Ado) are simultaneously produced via hydrolysis of S-adenosylhomocysteine (SAH), we hypothesized that hHcys may produce its pathogenic effects by decrease in plasma or tissue Ado concentrations.
Methods and Results— L-Hcys (1.5 µmol/min per kilogram) was infused intravenously for 60 minutes to produce acute hHcys in Sprague-Dawley rats. Plasma Hcys levels increased from 6.7±0.4 to 14.7±0.5 µmol/L, but Ado decreased from 141.7±15.1 to 52.4±6.8 nmol/L in these rats with acute hHcys. This hHcys-induced reduction of Ado was also observed in the kidney dialysate. In rats with chronic hHcys, plasma Ado levels were also significantly decreased. By kinetic analysis of the enzyme activities, decrease in renal Ado levels in hHcys was shown to be associated with inhibition of SAH hydrolase but not 5'-nucleotidase. Functionally, intravenous infusion of Hcys was found to decrease renal blood flow, glomerular filtration rate, and sodium and water excretion, which could be blocked by the Ado receptor antagonist 8-SPT.
Conclusions— These results strongly suggest that hHcys decreases plasma and tissue Ado concentrations associated with inhibition of SAH hydrolase. Decrease in plasma and tissue Ado may be an important mechanism mediating the pathogenic effects of Hcys.
Key Words: risk factors • hemodynamics • adenosine
This article has been cited by other articles:
 |
|
 |
|
  N. Li, L. Chen, R. W. Muh, and P.-L. Li Hyperhomocysteinemia Associated With Decreased Renal Transsulfuration Activity in Dahl S Rats Hypertension, June 1, 2006; 47(6): 1094 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Shoveller, J. A. Brunton, O. Brand, P. B. Pencharz, and R. O. Ball N-Acetylcysteine is a Highly Available Precursor for Cysteine in the Neonatal Piglet Receiving Parenteral Nutrition JPEN J Parenter Enteral Nutr, March 1, 2006; 30(2): 133 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Hansen, S. Hashimoto, M. Oppermann, Y. Huang, J. P. Briggs, and J. Schnermann Vasoconstrictor and Vasodilator Effects of Adenosine in the Mouse Kidney due to Preferential Activation of A1 or A2 Adenosine Receptors J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1150 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Herrmann, H. Schorr, R. Obeid, J. Makowski, B. Fowler, and M. K. Kuhlmann Disturbed Homocysteine and Methionine Cycle Intermediates S-Adenosylhomocysteine and S-Adenosylmethionine Are Related to Degree of Renal Insufficiency in Type 2 Diabetes Clin. Chem., May 1, 2005; 51(5): 891 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. H. Woo, Y. L. Siow, G. N. Pierce, P. C. Choy, G. Y. Minuk, D. Mymin, and K. O Hyperhomocysteinemia induces hepatic cholesterol biosynthesis and lipid accumulation via activation of transcription factors Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E1002 - E1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Riksen, G. A. Rongen, G. H.J. Boers, H. J. Blom, P. H.H. van den Broek, and P. Smits Enhanced Cellular Adenosine Uptake Limits Adenosine Receptor Stimulation in Patients With Hyperhomocysteinemia Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 109 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Baric, K. Fumic, B. Glenn, M. Cuk, A. Schulze, J. D. Finkelstein, S. J. James, V. Mejaski-Bosnjak, L. Pazanin, I. P. Pogribny, et al. S-adenosylhomocysteine hydrolase deficiency in a human: A genetic disorder of methionine metabolism PNAS, March 23, 2004; 101(12): 4234 - 4239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Hansen and J. Schnermann Vasoconstrictor and vasodilator effects of adenosine in the kidney Am J Physiol Renal Physiol, October 1, 2003; 285(4): F590 - F599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Zhang, Y.-F. Chen, D. X. Zhang, F.-X. Yi, J. Qi, P. Andrade-Gordon, L. de Garavilla, P.-L. Li, and A.-P. Zou Urotensin II is a nitric oxide-dependent vasodilator and natriuretic peptide in the rat kidney Am J Physiol Renal Physiol, October 1, 2003; 285(4): F792 - F798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Riksen, G. A. Rongen, H. J. Blom, F. G.M. Russel, G. H.J. Boers, and P. Smits Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia Cardiovasc Res, August 1, 2003; 59(2): 271 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Rensma, A. J. Apperloo, P. E. de Jong, Y.-F. Chen, P.-L. Li, and A.-P. Zou Why Does Elevated Plasma Homocysteine Result in Severe Microvascular Injury, but Not Glomerular Damage? * Response Circulation, March 25, 2003; 107 (11): e77 - e77. [Full Text] [PDF]
|
|