Johnson Fruzsina K, Teran Federico J, Prieto-Carrasquero Minolfa, Johnson Robert A
Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Am J Hypertens. 2002 Dec;15(12):1074-80. doi: 10.1016/s0895-7061(02)03062-5.
Vascular endothelium and smooth muscle express heme oxygenase (HO) that metabolizes heme to biliverdin, iron and carbon monoxide (CO). Carbon monoxide promotes endothelium-independent vasodilation, but also inhibits nitric oxide formation. This study examines the hypothesis that an inhibitor of HO promotes endothelium-independent vasoconstriction, which is attenuated in the presence of unabated nitric oxide formation.
In vivo studies were conducted in anesthetized male Sprague-Dawley (SD) rats instrumented with flow probes and arterial catheters. In vitro experiments were performed on pressurized first-order gracilis muscle arterioles isolated from male SD rats superfused with oxygenated modified Krebs buffer.
Vascular smooth muscle and endothelium showed positive HO-1 and HO-2 immunostaining. In anesthetized rats the HO inhibitor chromium mesoporphyrin (CrMP; 45 micromol/kg intraperitoneally) had minimal effect on hindlimb resistance. However, in animals pretreated with N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 mg/kg intraperitoneally), CrMP substantially increased hindlimb resistance. In contrast, in rats infused with phenylephrine to increase blood pressure and vascular tone, CrMP had no effect on hindlimb resistance. In isolated arterioles denuded of endothelium, CrMP (15 micromol/L) caused a powerful vasoconstriction, which was abolished in the presence of a functional endothelium. In arterioles with intact endothelium pretreated with L-NAME (1 mmol/L), or with L-NAME and sodium nitroprusside (10 to 30 nmol/L), CrMP promoted a similarly powerful vasoconstriction as in vessels denuded of endothelium.
These results suggest that smooth muscle-derived CO may contribute to endothelium-independent regulation of vascular tone by providing a vasodilatory influence. Furthermore, the dilatory effects of endogenous CO are offset by a unique interaction between the CO and nitric oxide systems.
血管内皮和平滑肌表达血红素加氧酶（HO），其可将血红素代谢为胆绿素、铁和一氧化碳（CO）。一氧化碳可促进非内皮依赖性血管舒张，但也会抑制一氧化氮的生成。本研究检验了以下假设：HO抑制剂可促进非内皮依赖性血管收缩，而在一氧化氮生成未受抑制的情况下这种收缩会减弱。
在麻醉的雄性Sprague-Dawley（SD）大鼠体内进行研究，这些大鼠安装了流量探头和动脉导管。体外实验在从雄性SD大鼠分离的一级股薄肌小动脉上进行，这些小动脉用含氧的改良 Krebs 缓冲液灌注并保持压力。
血管平滑肌和内皮显示HO-1和HO-2免疫染色阳性。在麻醉大鼠中，HO抑制剂中卟啉铬（CrMP；45微摩尔/千克腹腔注射）对后肢阻力影响极小。然而，在预先用N（ω）-硝基-L-精氨酸甲酯（L-NAME；300毫克/千克腹腔注射）处理的动物中，CrMP显著增加了后肢阻力。相反，在输注去氧肾上腺素以升高血压和血管张力的大鼠中，CrMP对后肢阻力无影响。在去除内皮的分离小动脉中，CrMP（15微摩尔/升）引起强烈的血管收缩，而在功能性内皮存在时这种收缩被消除。在用L-NAME（1毫摩尔/升）预处理的具有完整内皮的小动脉中，或在用L-NAME和硝普钠（10至30纳摩尔/升）预处理的小动脉中，CrMP促进了与去除内皮的血管中类似强烈的血管收缩。
这些结果表明，平滑肌衍生的CO可能通过提供血管舒张作用来促进对血管张力的非内皮依赖性调节。此外，内源性CO的舒张作用被CO和一氧化氮系统之间独特的相互作用所抵消。
