STRAIN INCREASES AIRWAY SMOOTH-MUSCLE CELL-PROLIFERATION

Airway smooth muscle (ASM) cell hyperplasia is a common finding in lun g diseases in which increased transpulmonary pressure is necessary for adequate ventilation. The extent to which mechanical deformation of A SM cells contributes to the observed hyperplastic changes has not been addressed. To determine if cyclic stretch alters ASM cell proliferati on and protein content in vitro, canine ASM cells were cultured on col lagen-coated silastic membranes, subjected to a stretch-relaxation reg imen, and compared with cultured cells on a rocking platform or with c ontrol (unmanipulated) cells. During the log phase of cell growth, cyc lic stretch resulted in increased cell numbers (P < 0.001). Incorporat ion of [H-3]thymidine ([H-3]TdR) was assessed after 5 or 14 days in cu lture during 12-h pulse in stretched, rocked, and control cells. Incor poration of [H-3]TdR per cell was elevated in stretched cells when com pared with either rocked or control cells at 5 days but not 14 days. T otal cellular protein content per well determined after cells had reac hed confluence was greater in stretched cells than in the controls (74 .2 +/- 7.9 stretched versus 49.1 +/- 5.6 control versus 51.1 +/- 6.5 r ocker; mug/10(5) cells; P < 0.05). Transmission electron microscopic o bservations of stretched cells suggested increased concentrations of m yofilaments compared with control cells. These observations suggest th at stretch may contribute to increased ASM hyperplasia and airway resi stance.