DIFFERENTIAL-EFFECTS OF PRESSURE AND FLOW ON DNA AND PROTEIN-SYNTHESIS AND ON FIBRONECTIN EXPRESSION BY ARTERIES IN A NOVEL ORGAN-CULTURE SYSTEM

Structural adaptation of the blood vessel wall occurs in response to m echanical factors related to blood pressure and flow. To elucidate the relative roles of pressure, flow, and medium composition, we have dev eloped a novel organ culture system in which rabbit thoracic aorta, he ld at in vivo length, can be perfused and pressurized at independently varied flow and pressure for several days. Histology and histomorphom etry, as well as scanning electron microscopy, revealed a well-preserv ed wall structure. In arteries perfused and pressurized at 80 mm Hg, e ndothelial injury led to a 2-fold increase in [H-3]thymidine incorpora tion in the media, which peaked at 3 to 5 days and returned to baselin e level at 6 to 8 days. In intact endothelialized vessels cultured for 3 days under no-flow conditions, pressure per se had no effect on DNA synthesis. In contrast, in the presence of serum, total protein synth esis, as assessed by [S-35]methionine incorporation into the media, wa s enhanced 6-fold at 150 mm Hg compared with vessels pressurized at 0 or 80 mm Hg. In intact vessels perfused at a constant flow of 40 mL/mi n for 3 days, DNA synthesis was unchanged regardless of the pressure l evel when vessels were cultured in the presence of serum but increased 8-fold at both 80 and 150 mm Hg in the absence of serum. Unlike DNA. synthesis, total protein synthesis was enhanced 12-fold by flow regard less of the presence or absence of serum. Expression of fibronectin wa s markedly enhanced at high transmural pressure, and serum potentiated its expression in the arterial wall. This never organ culture system of perfused and pressurized vessels allowed identification of differen tial effects of pressure, flow, and serum on DNA and total protein syn thesis, including cellular fibronectin expression.