Smooth muscle cell changes during flow-related remodeling of rat mesenteric resistance arteries

To obtain information on the molecular and cellular mechanisms of flow-indu ced arterial remodeling, we analyzed the morphology and smooth muscle cell (SMC) characteristics in rat mesenteric resistance arteries after intervent ions that decreased and increased flow. Juvenile male Wistar Kyoto rats wer e subjected to surgery that, compared with control arteries, provided arter ies with chronic low flow and chronic high flow. Low flow resulted in a dec reased passive lumen diameter, hypotrophy of the artery wall, and both loss and decreased size of SMCs. Time course studies, with intervention length ranging from 2 to 32 days of altered blood flow, showed that the narrowing of the lumen diameter in low-flow arteries appeared within 2 days and that an early dedifferentiation of SMC phenotype was indicated by markedly reduc ed levels of desmin mRNA. High flow resulted in an increased passive lumen diameter and in hypertrophy of the artery wall. The hypertrophy resulted fr om SMC proliferation because SMC number, measured by the 3D-dissector techn ique, was increased and immunohistochemical assessment of proliferating cel l nuclear antigen also showed an increase. The widening of high-flow arteri es required 16 days to become established, at which time desmin mRNA was re duced. This time was also required to establish changed wall mass in both l ow-flow and high-flow arteries. Apoptotic cells detected by TdT-mediated dU TP-biotin nick end labeling staining were mainly located in the medial laye r, and evaluation of DNA fragmentation indicated that increased apoptosis o ccurred in both low flow and high flow. This study shows for the first time direct evidence that reduced and elevated blood flow in resistance arterie s produce, respectively, decrease and increase in SMC number, with dediffer entiation of the SMCs in both cases.