IS SMOOTH-MUSCLE GROWTH IN PRIMATE ARTERIES REGULATED BY ENDOTHELIAL NITRIC-OXIDE SYNTHASE

Purpose: We investigated whether control of constitutive endothelial c ell nitric oxide synthase (cNOS) and nitric oxide (NO) by changes in s hear stress might be important for the regulation of smooth muscle cel l (SMC) growth and vascular diameter. Methods: Bilateral femoral arter iovenous fistulas were placed in baboons to increase the blood flow in the external iliac arteries. At 2 months, the fistula was ligated on one side to restore normal flow (flow switch). Results: In response to flow switch and a decrease in shear stress, iliac artery lumenal area decreased and SMC proliferation was induced. A decline in NO producti on, cNOS messenger RNA (mRNA), and protein were associated with these biological effects. In a subset of animals with iliac arteries under h igh flow infusion of No-nitro-L-arginine, an inhibitor of cNOS, did no t induce proliferation. Conclusion: Shear stress can regulate cNOS, va soconstriction, and SMC proliferation. A decrease in nitric oxide may be necessary, but is not sufficient to induce SMC proliferation in res ponse to a decrease in blood flow.