Sudesh Vasdev

HYPERTENSION RESEARCH

Role of methylglyoxal and advanced glycation end products in hypertension

Dr. Vasdev was the first to suggest that excess endogenous aldehydes, especially methylglyoxal, are the cause of essential hypertension. Hypertensive humans and rats show insulin resistance and impaired glucose metabolism. This altered glucose metabolism leads to production of highly reactive aldehydes, including methylglyoxal. These aldehydes react non-enzymatically with sulfhydryl and amino groups of proteins forming aldehyde conjugates, thus altering protein structure and function. Aldehyde conjugates, also known as advanced glycation end products (AGEs), have the capacity to adversely influence the function and expression of many of the body’s proteins including calcium channels, metabolic and antioxidant enzymes, receptors and structural proteins. Dr. Vasdev has shown that glucose and fructose, precursors of aldehydes, when given chronically to WKY rats caused hypertension, increased cytosolic [Ca²⁺]i, vascular Ca²⁺ uptake, tissue aldehydes and adverse renal vascular changes. In addition, he has shown that aldehydes (methylglyoxal, glyceraldehyde) and disulfiram, an inhibitor of aldehyde dehydrogenase, given in the diet of WKY rats, produces the same effects. These studies are of major clinical significance in that they identify what could be an important factor in the cause of human essential hypertension. More recently, along with his colleague Dr. Edward Randell, Dr. Vasdev has shown higher levels of methylglyoxal and specific AGEs in plasma of human diabetics using a Tandem Mass-spectrophotometric method. These methods will also be used as part of his ongoing research to identify specific AGEs in hypertensive animals, the mechanism by which they cause hypertension, and how AGE formation can be prevented using nutrients.

Non-pharmacologic approach to prevent hypertension

Dr. Vasdev has investigated the antihypertensive effects of nutrients using various hypertensive rat models. He has shown that dietary supplementation with lipoic acid, cysteine, vitamins B6, C and E, and low ethanol were effective in normalizing or attenuating blood pressure, cytosolic free calcium and AGEs. These studies have important implications for treatment of hypertension in humans.

Dr. Vasdev’s research has been funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation, and the Kidney Foundation of Canada.

Recent Publications

1. Ahmed A. Mostafa, Edward W. Randell, Sudesh C. Vasdev, Vicki D. Gill, Yingchun Han, Vereesh Gadag, Ahmed A. Raouf, Hala El Said. Plasma protein advanced glycation end products, arboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes. Molecular and Cellular Biochemistry DOI: 10.1007/s11010-007-9422-9

2. Sudesh Vasdev, D.V.M., PH.D., F.A.C.B., Vicki Gill, R.T. Antioxidants in the Treatment of Hypertension. International Journal of Angiology 14:60-73, 2005

3. Sudesh Vasdev, Carol AnnFord, Linda Longerich, Veeresh Gadag and S. Wadhawan. Role of aldehydes in fructose induced hypertension. Molecular and Cellular Biochemistry 181:1-9, 1998.

4. S. Vasdev, T. Mian, C.A. Ford, L. Longerich and S. Parai. Role of endogenous aldehydes in spontaneously hypertensive and disulfiram-induced hypertensive rats. Nutrition Metabolism and Cardiovascular Disease 6: 130-140, 1996

5. Sudesh Vasdev, Vicki Gill, Sushil Parai and Veerest Gadag. Low ethanol intake prevents salt-induced hypertension in WKY rats. Molecular and Cellular Biochemistry 2006 DOI: 10.1007/s11010-005-9058-6

6. Sudesh Vasdev, Carol Ann Ford, Linda Longerich, Sushil Parai and Veeresh Gadag. Antihypertensive effect of low ethanol intake in spontaeously hypertensive rats. Molecular and Cellular Biochemistry 200:85-92, 1999

7. Sudesh Vasdev, Vicki Gill, Pawan K. Singal. Beneficial effect of low ethanol intake onthe cardiovascular system: possible biochemical mechanisms. Vascular Health and Risk Management 2(3) 263-276, 2006

8. Sudesh, Vasdev, Vicki Gill, Sushil Parai, and Vereesh Gadag. Fructose-induced hypertension in Wistar-Kyoto rats: Interation with moderately high dietary salt. Canadian Journal of Physiolology Pharmacology 85: 1-9, 2007

9. Sudesh, Vasdev, Linda Longerich, and Vicki Gill. Prevention of fructose-induced hypertension by dietary vitamins. Clinical Biochemistry 37: ) 1-9, 2004

10. Sudesh, Vasdev and Vicki Gill. Hypertension and Atherosclerosis: Advanced Glycation End Products—A Common Link. In: Biochemistry of Atherosclerosis (eds Cheema, SK, et al) 305-326, 2006

11. Sudesh, Vasdev, Vicki Gill, Sushil Parai and Veeresh Gadag. Dietary lipoic acid supplementation attenuates hypertension in Dahl salt sensitive rats. Molecular and Cellular Biochemistry 275: 135-141, 2005

12. Sudesh, Vasdev, Vicki Gill, Linda Longerich, Sushil Parai and Veeresh Gadag. Salt-induced hypertension in WKY rats: Prevention by α-lipoic acid supplementation. Molecular and Cellular Biochemistry 254: 319-326, 2003

13. Sudesh, Vasdev, Carol Ann Ford, Sushil Parai, Linda Longerich and Veeresh Gadag. Dietary α-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. Journal of Hypertension 18: 557-573, 2000.

14. Sudesh, Vasdev. The antihypertensive effect of lipoic acid. Hypertension Canada 80: 6-7, 2004

15. S Vasdev, CA Sampson and VM Prabhakaran. Platelet-free calcium and vascular calcium uptake in ethanol-induced hypertensive rats. Hypertension 18: 116-122, 1991

16. Sudesh Vasdev, Pawan Singal and Vicki Gill. Vitamin E and Blood Pressure. In: The Encyclopedia of Vitamin E (eds V.R. Preedy and R.R. Watson) © CAB International 633-643, 2006

17. S. Vasdev, C.A. Ford, S. Parai, L. Longerich and V. Gadag. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Molecular and Cellular Biochemistry 100: 155-162, 1999

18. S. Vasdev, C.A. Ford, S. Parai, L. Longerich and V. Gadag. Dietary vitamin C supplementation lowers blood pressure in spontaneously hypertensive rats. Molecular and Cellular Biochemistry 218: 97-103, 2001

19. S. Vasdev, V. Gill, S. Parai, L. Longerich and V. Gadag. Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats. Molecular and Cellular Biochemistry 241: 107-114, 2002

20. S. Vasdev, V. Gill, S. Parai, L. Longerich and V. Gadag. Dietary vitamin E supplementation lowers blood pressure in spontaneously hypertensive rats. Molecular and Cellular Biochemistry 238: 111-117, 2002