Interaction between Flow-Induced Prostacyclin Production and Nitric Oxide Synthesis in Vascular Smooth Muscle Cells.

Abstract

The interaction between flow-induced prostacyclin production and nitric oxide (NO) synthesis in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) was studied. Flow was made by 3 cm-amplitude horizontal shaking at various frequencies at 37 °C under 5% CO 2 and 95% air. Basal prostacyclin and NO production rates did not differ between strains. Prostacyclm production during flow was significantly greater with increasing shear stress from shaking frequencies of 120/min to 180/min, and was greater in SHR than in WKY. In contrast, flow-induced NO production was greater in WKY than in SHR. The addition of N nitro-L-arginine further increased the flow-induced increase in the production of prostacyclin in WKY in a dose-dependent manner, but had no effects in SHR. Indomethacin did not affect flow-induced NO production in either strain. We conclude that increases in prostacyclin production in SHR-derived VSMC during shear stress may be due to decreases in the suppression by NO and may compensate for hypertension.(Hypertens Res 1994;17: 227-232) Key Words: spontaneously hypertensive rat, shear stress, prostacyclin, nitric oxide, vascular smooth muscle cell Prostacyclin, a potent vasodilator and the most potent endogenous inhibitor of platelet aggregation known, is synthesized from arachidonic acid (AA) in many types of cells. In vascular endothelial cells, mechanical forces associated with blood flow, such as shear stress and pressure-stretch, are known to stimulate prostacyclin production(1), and play an important role in the regulation of vascular tone (2), vascular remodeling (3), and the focal development of atherosclerotic lesions (4) . Shear stress also stimulates the production of nitric oxide (NO) via a shear-sensitive K current (5,6) in endothelial cells. Although previous studies of the effect of shear stress on prostacyclin or NO production were focused on vascular endothelial cells, vascular smooth muscle cells (VSMC) are also exposed to shear stress, such as blood flow when intima is exfoliated, and interstitial fluid flow during skeletal muscle contraction or relaxation. Moreover, previous evidence (7,8) has shown that shear stress caused by blood flow displaces the inner layers of the artery wall in the direction of flow as well as the endothelium, and that ion transport is more sensitive to shear in VSMC than in several other types of cells, including endothelial cells.Previous studies have shown that in VSMC shear stress opens nitrendipine-sensitive calcium channels (8), stimulates cell growth (9), and induces endocytosis of large amounts of extracellular sodium and cholesterol (9). Recent evidence (10) has shown that shear stress reduces the 24-hour incorporation of tritiated thymidine and cell proliferation. However, none of those studies addressed the effects of shear stress on production of prostacyclin and NO in VSMC. Because recent evidence (11) has shown that these compounds are also synthesized in VSMC and regulate the proliferation rates and ...

A Novel Inhibitory Effect on Prostacyclin Synthesis of Coupling Factor 6 Extracted from the Heart of Spontaneously Hypertensive Rats

“…Because prostacyclin receptor is expressed in many tissues such as aorta, lung, atrium, ventricle, and kidney (20), and because PG transporter (12) does not mediate the vascular clearance of prostacyclin, the endogenous prostacyclin synthe- sis inhibitory peptide may have inhibitory effects against widespread biological actions of prostacyclin. This peptide also may counteract a biological action of AA such as inhibition of voltage-gated Ca 2ϩ current, because a major acting site of coupling factor 6 is the inhibition of AA release from the plasma membrane.…”

“…The cells were washed twice with serum-free DMEM and incubated in 250 l of serumfree DMEM in the presence or absence of crude extract (10 g protein/ ml) at 37°C. After 30 min, the medium was collected and the concentration of 6-keto-PGF 1␣ was measured by direct radioimmunoassay in duplicate, as reported previously (20).…”

Simultaneous Intravascular Two-Dimensional Plus Doppler Ultrasound Is Useful for Evaluation of Postischemic Vasodilatation: Plasma NOx- Levels Determined by the Griess Method May Not Reflect the Extent of Postischemic NO-Induced Vasodilatation.

“…It is possible, however, intravascular two-dimensional ultrasound imaging is available and is suitable not only for morphologic evaluation of the arterial wall (12) but for the assessment of vasomotion (13). Thus, the aim of this study was 1) to accurately assess postischemic vasodilatation by changes in CSA using simultaneous intravascular two-dimensional and Doppler ultrasound (14,15) and 2) to clarify whether plasma nitrite and nitrate (NOX-) levels (16)(17)(18), as stable NO metabolites, change during postischemic vasodilatation in this animal model.…”