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 homeostasis is maintained through the cross talk of shear-induced production of prostacyclin and nitric oxide (NO) in vascular smooth muscle cells (VSMC). Confluent A7r5 cells derived from rat aortic VSMC and mesenteric VSMC were exposed 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 synthase protein was expressed after shear stress in both types of VSMC. Inhibition 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 monocytes was suppressed by 50% after shear stress. This suppression was abolished by pretreatment with 10(-4) M of indomethacin, whereas inhibition of NO synthase only minimally inhibited it. We conclude that there is a cross talk of shear-induced production of prostacyclin and NO in VSMC. At sites of vascular damage, prostacyclin synthesis may prevent monocyte adhesiveness for VSMC through the concomitant enhancement of NO production.
Osanai
T
T
Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, 036-8562 Japan. osanait@cc.hirosaki-u.ac.jp
Akutsu
N
N
Fujita
N
N
Nakano
T
T
Takahashi
K
K
Guan
W
W
Okumura
K
K
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology*; D008642:Mesenteric Veins / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013314:Stress, Mechanical
D009569:Nitric Oxide; D011464:Epoprostenol