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.

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Hypertension is commonly observed in alcoholics. Both the renin-angiotensin system and the non-renin-angiotensin system (NRAS) have been implicated in the dynamics for the maintenance of blood pressure. Acetaldehyde has earlier been reported to enhance the generation of the rate-limiting angiotensin I (Ang I) in bilaterally nephrectomized rat plasma and to inhibit the activity of several angiotensinases (A, B, and M) in human serum, thereby promoting a hypertensive set of reactions. In the current study, the effect of acetaldehyde upon cathepsin G and mast cell chymase has been investigated. Acetaldehyde at 223.5 down to 11.2 mM concentrations enhanced cathepsin G activity at all levels employed 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, it is suggested 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. Mast cell chymase activity also is elevated upon exposure to 440 mM acetaldehyde and is diminished with 27 mM acetaldehyde. Since both enzymes also degrade Ang II, degradative effects may be partially neutralized.

Captopril, a thiol-containing antihypertensive drug, and lisinopril, an amino-containing antihypertensive drug, will both prolong the prothrombin time (PT) of Level I plasma. Acetaldehyde, a product of ethanol metabolism, also prolongs PT. In a study to examine the interrelationship between hypertension, hemostasis, and alcoholism, an examination of the impact of acetaldehyde on the effects of captopril and lisinopril upon PT was undertaken. It was observed that the pre-mixing of 7.7 x 10(-3) M captopril with 40.6 mM acetaldehyde for 30 min at R.T. prior to the addition to plasma results in a prolongation of PT which is less than that caused by acetaldehyde alone. Successive additions of captopril and acetaldehyde to plasma also yield a PT which is less than that of acetaldehyde alone. These data suggest that captopril may partially inactivate and detoxify the acetaldehyde effect on hemostasis upon interaction to form a thiohemiacetal. Captopril may prolong PT by the reduction of the S-S bridges in the coagulation factors. Lisinopril behaves similarly to captopril, prolonging PT. Successive additions of lisinopril and acetaldehyde, or pre-mixtures thereof, to plasma result in a lesser prolongation of clotting time relative to acetaldehyde alone. Since primary amines similar to that of lisinopril readily form Schiff bases with acetaldehyde, these data suggest that both captopril and lisinopril may act to detoxify the acetaldehyde effect upon plasma, albeit by different mechanisms.