在高血压大鼠的骨骼肌小动脉中，一氧化氮和前列腺素介导的反应均受损。

Both nitric oxide and prostaglandin-mediated responses are impaired in skeletal muscle arterioles of hypertensive rats.

作者信息

Huang A, Koller A

机构信息

Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.

出版信息

J Hypertens. 1996 Jul;14(7):887-95. doi: 10.1097/00004872-199607000-00012.

DOI:10.1097/00004872-199607000-00012

PMID:8818928

Abstract

OBJECTIVE

To investigate the role played by endothelium-derived dilator factors in the regulation of peripheral vascular resistance by determining whether the dysfunction of the endothelium contributes to the reduced dilator responsiveness of skeletal muscle arterioles in hypertension.

METHODS

The endothelial function of isolated, cannulated, pressurized (at 80 mmHg) gracilis muscle arterioles (45-50 microns diameter) of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) was compared by utilizing vasoactive agents of known action.

RESULTS

Acetylcholine (ACh, 10(-9), 10(-8) and 5 x 10(-8) mol/l) and sodium nitroprusside (SNP, 10(-8), 10(-7) and 10(-6) mol/l) elicited similar dilations in arterioles of WKY rats and SHR. Substance P (10(-9), 10(-8) and 5 x 10(-8) mol/l) caused significantly less dilation (by approximately 70%) of SHR arterioles compared with WKY rat arterioles. The calcium ionophore A23187 (5 x 10(-8), 5 x 10(-7) and 10(-6) mol/l) elicited dilations in WKY rat arterioles (9.1 +/- 1.1, 24.0 +/- 1.5, and 39.0 +/- 3.4%, respectively), whereas it evoked constrictions (6.5 +/- 1.1, 14.9 +/- 1.5, and 25.5 +/- 1.6%, respectively) in SHR arterioles. Removal of endothelium, inhibition of prostaglandin synthesis (indomethacin) or blockade of prostaglandin H2 (PGH2) receptors (by SQ 29548) eliminated A23187-induced constrictions of SHR arterioles. The nitric oxide synthase blocker, NG-nitro-L-arginine elicited a significantly greater inhibition of substance P-induced dilations and a greater reduction in basal diameter of WKY rat arterioles than it did in those from SHR.

CONCLUSIONS

These data suggest that, in SHR arterioles, the synthesis and/or action of nitric oxide is, or are, impaired and the metabolism of arachidonic acid is altered, resulting in an enhanced production of PGH2. The simultaneous dysfunction of these two dilator pathways of arteriolar endothelium could contribute significantly to the enhanced peripheral resistance observed in hypertension.

摘要

目的

通过确定内皮功能障碍是否导致高血压患者骨骼肌小动脉扩张反应性降低，来研究内皮源性舒张因子在调节外周血管阻力中所起的作用。

方法

利用已知作用的血管活性药物，比较正常血压的Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）分离的、插管的、加压（80 mmHg）的股薄肌小动脉（直径45 - 50微米）的内皮功能。

结果

乙酰胆碱（ACh，10⁻⁹、10⁻⁸和5×10⁻⁸ mol/L）和硝普钠（SNP，10⁻⁸、10⁻⁷和10⁻⁶ mol/L）在WKY大鼠和SHR的小动脉中引起相似的扩张。与WKY大鼠小动脉相比，P物质（10⁻⁹、10⁻⁸和5×10⁻⁸ mol/L）引起SHR小动脉的扩张明显减少（约70%）。钙离子载体A23187（5×10⁻⁸、5×10⁻⁷和10⁻⁶ mol/L）在WKY大鼠小动脉中引起扩张（分别为9.1±1.1%、24.0±1.5%和39.0±3.4%），而在SHR小动脉中引起收缩（分别为6.5±1.1%、14.9±1.5%和25.5±1.6%）。去除内皮、抑制前列腺素合成（吲哚美辛）或阻断前列腺素H2（PGH2）受体（通过SQ 29548）可消除A23187诱导的SHR小动脉收缩。一氧化氮合酶阻滞剂NG-硝基-L-精氨酸对P物质诱导的WKY大鼠小动脉扩张的抑制作用明显大于对SHR小动脉的抑制作用，且对WKY大鼠小动脉基础直径的降低作用也更大。