[Apoptosis and necrosis induced by cyclic mechanical stretching in alveolar type-II-cells--influence of captopril and L-Arginine].
BACKGROUND
Alveolar type-II(ATII)-cells are exposed to mechanical stretch during breathing and mechanical ventilation. Increased stretch may contribute to lung injury.


METHODS
The influence of three stretching patterns (characterized by frequency [min (-1)] - increase in surface area [%]: S40 - 13, S60 - 13, S40 - 30) on parameters of apoptosis, necrosis and membrane integrity in rat ATII cells was compared with that in static cultures. The S40 - 13 stretching pattern simulated normal breathing. The other patterns were chosen to study increased amplitude and frequency.


RESULTS
There were no significant differences between the S40 - 13 group and static cultures. LDH release and early apoptotic cells were significantly increased in S60 - 13 and S40 - 30 in comparison with static cultures (LDH: 0.089 +/- 0.014 microg/ml and 0.177 +/- 0.050 microg/ml versus 0.050 +/- 0.011 microg/ml; early apoptosis: 17 +/- 3.5 % and 23 +/- 3.1 % versus 9.7 +/- 1.4 %) at 24 h. Necrosis was significantly increased only in the S40-30 group (13 +/- 2.4 % versus 6.1 +/- 0.9 % in static culture at 24 h). Captopril as well as L-Arginine prevented apoptosis and reduced apoptotic cells to static culture levels in the S40 - 30 group but did not influence necrosis and LDH release.


CONCLUSIONS
Increased mechanical stretch may contribute to lung injury by induction of apoptosis and necrosis in ATII cells. Apoptosis induced by high amplitude mechanical stretch is prevented by captopril and L-Arginine.
Hammerschmidt
S
S
Pneumologie, Medizinische Klinik I, Universität Leipzig, Johannisallee 32, 04103 Leipzig, Germany. stefan.hammerschmidt@t-online.de
Kuhn
H
H
Grasenack
T
T
Gessner
C
C
Wirtz
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D008297:Male; D009336:Necrosis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D000806:Angiotensin-Converting Enzyme Inhibitors; D001120:Arginine; D002216:Captopril