Johns D G, Dorrance A M, Tramontini N L, Webb R C
Department of Physiology, Medical College of Georgia, Augusta 30912-3000, USA.
Exp Biol Med (Maywood). 2001 Jan;226(1):27-31. doi: 10.1177/153537020122600104.
Tetrahydrobiopterin (BH4) acts as an important co-factor for endothelial nitric oxide synthase (eNOS). Glucocorticoids have been shown to inhibit expression of the rate-limiting enzyme for tetrahydrobiopterin synthesis, GTP cyclohydrolase, in other cell types. We hypothesized that endothelium-dependent vasodilator responses would be blunted in rats made hypertensive with dexamethasone. Further, we hypothesized that treatment of rat vascular segments with dexamethasone would result in attenuation of endothelial function accompanied by decreased GTP cyclohydrolase expression. We report that endothelium-dependent relaxation responses to the calcium ionophore A23187 are reduced in aortic rings from dexamethasone-hypertensive rats compared with sham values. Dexamethasone incubation abolishes contraction to Nomega-nitro-L-arginine (L-NNA, 10(-5) M) in endothelium-intact aortic rings, and inhibits expression of GTP cyclohydrolase. We conclude that inhibition of BH4 synthesis by glucocorticoid regulation of GTP cyclohydrolase expression may contribute to reduced endothelium-dependent vasodilation characteristic of glucocorticoid-induced hypertension.
四氢生物蝶呤（BH4）是内皮型一氧化氮合酶（eNOS）的重要辅助因子。在其他细胞类型中，糖皮质激素已被证明可抑制四氢生物蝶呤合成的限速酶——GTP环化水解酶的表达。我们推测，用 dexamethasone使大鼠患高血压后，内皮依赖性血管舒张反应会减弱。此外，我们推测用 dexamethasone处理大鼠血管段会导致内皮功能减弱，同时伴有GTP环化水解酶表达降低。我们报告，与假手术组相比，dexamethasone诱导高血压大鼠主动脉环对钙离子载体A23187的内皮依赖性舒张反应降低。dexamethasone孵育消除了内皮完整主动脉环对Nω-硝基-L-精氨酸（L-NNA，10^(-5) M）的收缩反应，并抑制了GTP环化水解酶的表达。我们得出结论，糖皮质激素通过调节GTP环化水解酶表达来抑制BH4合成，这可能是糖皮质激素诱导的高血压所特有的内皮依赖性血管舒张减少的原因。
