Cross talk between prostacyclin and nitric oxide under shear in smooth muscle cell: role in monocyte adhesion

We tested the hypothesis that at sites of vascular damage, vessel homeostas is is maintained through the cross talk of shear-induced production of pros tacyclin and nitric oxide (NO) in vascular smooth muscle cells (VSMC). Conf luent A7r5 cells derived from rat aortic VSMC and mesenteric VSMC were expo sed to shear stress at 15 dyn/cm(2) for 90 min with the use of a cone-plate device, and productions of prostacyclin and NO were examined. Shear stress increased cumulative production of prostacyclin by 3- to 3.5-fold and that of NO by 6- to 7.5-fold. Western blot analysis showed that inducible NO sy nthase protein was expressed after shear stress in both types of VSMC. Inhi bition of NO synthase enhanced the shear-induced production of prostacyclin from 40 to 60%. Shear-induced production of NO was suppressed by 70% after treatment with 10(-4) M of indomethacin. A7r5 cells adhesiveness for monoc ytes was suppressed by 50% after shear stress. This suppression was abolish ed by pretreatment with 10(-4) M of indomethacin, whereas inhibition of NO synthase only minimally inhibited it. We conclude that there is a cross tal k of shear-induced production of prostacyclin and NO in VSMC. At sites of v ascular damage, prostacyclin synthesis may prevent monocyte adhesiveness fo r VSMC through the concomitant enhancement of NO production.