Inhibitory effect of the angiotensin converting enzyme inhibitors captopril and enalapril on the conversion of procollagen to collagen.
OBJECTIVE
Angiotensin converting enzyme inhibitors are reported to inhibit the collagen accumulation involved in left ventricular hypertrophy. We tested the effect of captopril and enalapril on the conversion of procollagen to collagen in short-term tissue cultures in order to study the possible mechanisms by which the antifibrotic effect of this group of inhibitors takes place.


METHODS
We employed short-term cartilage and tendon tissue cultures to monitor the conversion of procollagen to collagen. After pulse-labelling with [14C]-proline, the cultures were incubated further with the test compounds in different concentrations for a 180 min chase period. The reaction was stopped and radioactive collagenous peptides were analysed by gel electrophoresis. The amounts of collagenous proalpha and alpha chains were estimated, and the inhibition of procollagen to collagen conversion was calculated relative to 0 min control (100% inhibition) and 180 min control (0% inhibition) samples.


RESULTS
Inhibition (50%) was obtained with 7 mmol/l captopril and 22 mmol/l enalapril in the cartilage cultures. Both compounds seemed to inhibit the conversion in clearly lower concentrations in tendon cultures, 4 mmol/l and 7 mmol/l, respectively, were sufficient for 50% inhibition. Angiotensin I, II, saralasin and bradykinin did not have any effect on conversion at 3.5, 9, 2 and 4 mmol/l concentrations, respectively.


CONCLUSIONS
The peptidase inhibitors captopril and enalapril are able to inhibit the conversion of procollagen to collagen, which is a proteolytic process, possibly by inhibiting the specific procollagen proteases. Whether this phenomenon is involved in the antifibrotic property of angiotensin converting enzyme inhibitors warrants further study, as does the question of whether new antifibrotic agents could be developed on this basis.
Männistö
T K
TK
Department of Medical Biochemistry, University of Oulu, Oulu, Finland.
Karvonen
K E
KE
Kerola
T V
TV
Ryhänen
L J
LJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002356:Cartilage / Q000378:metabolism; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis*; D046508:Culture Techniques; D004656:Enalapril / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D011347:Procollagen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013710:Tendons / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; C093212:procollagen type II carboxy-terminal peptide; D004656:Enalapril; D003094:Collagen; D002216:Captopril