Effect of acetaldehyde upon cathepsin G and chymase. NRAS implications.
Hypertension is commonly observed in alcoholics. Both the renin-angiotensin system (RAS) and the non-renin-angiotensin system (NRAS) have been implicated in the dynamics of blood pressure maintenance. In bilaterally nephrectomized rats, acetaldehyde has been reported to enhance the generation of the rate-limiting angiotensin I (ANG I) in the plasma, and in humans it inhibits the activity of several angiotensinases (A, B, and M) in the serum, thereby promoting a hypertensive set of reactions. We report here the results of a study on the effect of acetaldehyde upon cathepsin G and mast cell chymase. Acetaldehyde enhanced cathepsin G activity at all of the concentrations tested between 11.2 and 223.5 mM in a statistically significant manner. Since cathepsin G is one of several enzymes transforming ANG I into ANG II and is also capable of cleaving ANG II directly from angiotensinogen, we suggest that alcoholism, which will generate exogenous acetaldehyde from ingested alcohol, may be a contributory factor for an elevated cathepsin G activity and, consequently, hypertension via the NRAS. Chymase activity also is elevated in the presence of 440 mM acetaldehyde and diminished in the presence of 27 mM acetaldehyde. Since both enzymes also degrade ANG II, the degradative effects of each enzyme on ANG II may neutralize one another.
Brecher
Arthur S
AS
Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, USA. artbrec@bgsu.edu
Dubord
Rachel
R
D000079:Acetaldehyde / Q000494:pharmacology*; D000437:Alcoholism / Q000097:blood / Q000503:physiopathology; D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000187:drug effects*; D053818:Chymases / Q000187:drug effects*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology; D051381:Rats; D012084:Renin-Angiotensin System; D012697:Serine Endopeptidases / Q000187:drug effects*
D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534097:Ctsg protein, rat; D053818:Chymases; D000079:Acetaldehyde