Collins L C, Roberts A M
Critical Care, University of Louisville School of Medicine, Louisville, Kentucky, 40292, USA.
Microvasc Res. 1997 Jan;53(1):63-72. doi: 10.1006/mvre.1996.1992.
Platelet-activating factor (PAF) causes altered vascular tone in the mesenteric, pulmonary, and skeletal muscle vascular beds, enhanced macromolecular leak in postcapillary venules, and bronchoconstriction. In spontaneously breathing, anesthetized male Sprague-Dawley rats, we examined responses of individual tracheal microvessels using intravital video microscopy with epi-illumination using a polarizing filter and a long working distance lens (10x). Topical application of PAF (0.1 ml; 10(-9), 10(-7), or 10(-5) M) caused venules (diameter, 51 +/- 5 microm, mean +/- SEM) to constrict in a concentration-dependent fashion. Venoconstriction began within 0-3 min and was maximal within 10 min. In contrast, PAF (10(-5) M) applied to arterioles (diameters, 37 +/- 1 microm) ultimately caused constriction by 21 +/- 7%, but in three dilation (38 +/- 9%) occurred first. PAF (10(-7) and 10(-9) M) applied to arterioles (diameter 36 +/- 3 and 38 +/- 3 microm, respectively) caused no significant change in diameter. Infusion of BN52021, a PAF receptor antagonist, completely blocked constriction of venules and arterioles to PAF (10(-5) M), but dilation (17 +/- 0.2%) still occurred in three of five arterioles. Infusion of Nomega-nitro-l-arginine methyl ester (L-NAME; 1 mg/kg/min), a nitric oxide (NO) synthase inhibitor, potentiated venoconstriction by 34 +/- 18% in response to PAF (10(-7) M) and blocked arteriolar dilation to PAF (10(-5) M). Arteriolar constriction was unaffected by inhibiting NO release. Topical application of L-NAME (10(-3) M) constricted venules (n = 6) by 13 +/- 2% and arterioles (n = 5) by 26 +/- 4%. Venules constricted 33 +/- 15% less to PAF (10(-7) M, n = 5) following topical L-NAME (33 +/- 15%) than with infused l-NAME. Arterioles (n = 5) constricted 27 +/- 4% to PAF (10(-5) M) after topical l-NAME, no different from the group receiving infused L-NAME. We conclude that (1) PAF has a greater vasoconstrictive effect on tracheal venules than arterioles; (2) arterioles have a biphasic response to PAF at some concentrations; (3) PAF-induced vasoconstriction, but not dilation, is receptor mediated; (4) nitric oxide attenuates tracheal venoconstriction and may cause arteriolar dilation in response to PAF; and (5) endogenous release of NO appears to modulate the basal tone of tracheal arterioles more than venules.
血小板活化因子（PAF）可引起肠系膜、肺和骨骼肌血管床血管张力改变，毛细血管后微静脉中大分子渗漏增加，以及支气管收缩。在自主呼吸的麻醉雄性Sprague-Dawley大鼠中，我们使用配备偏振滤光片和长工作距离镜头（10倍）的落射照明活体视频显微镜检查了单个气管微血管的反应。局部应用PAF（0.1毫升；10⁻⁹、10⁻⁷或10⁻⁵摩尔/升）可使微静脉（直径51±5微米，平均值±标准误）以浓度依赖方式收缩。静脉收缩在0 - 3分钟内开始，10分钟内达到最大程度。相比之下，将PAF（10⁻⁵摩尔/升）应用于小动脉（直径37±1微米）最终导致收缩21±7%，但有三次先出现扩张（38±9%）。将PAF（10⁻⁷和10⁻⁹摩尔/升）应用于小动脉（直径分别为36±3微米和38±3微米）未引起直径的显著变化。输注PAF受体拮抗剂BN52021可完全阻断微静脉和小动脉对PAF（10⁻⁵摩尔/升）的收缩，但五只小动脉中有三只仍出现扩张（17±0.2%）。输注一氧化氮（NO）合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME；1毫克/千克/分钟）可使对PAF（10⁻⁷摩尔/升）的静脉收缩增强34±18%，并阻断小动脉对PAF（10⁻⁵摩尔/升）的扩张。抑制NO释放对小动脉收缩无影响。局部应用L-NAME（10⁻³摩尔/升）可使微静脉（n = 6）收缩13±2%，小动脉（n = 5）收缩26±4%。局部应用L-NAME（33±15%）后，微静脉对PAF（10⁻⁷摩尔/升，n = 5）的收缩比输注L-NAME时少33±15%。局部应用L-NAME后，小动脉（n = 5）对PAF（10⁻⁵摩尔/升）收缩27±4%，与接受输注L-NAME的组无差异。我们得出结论：（1）PAF对气管微静脉的血管收缩作用比对小动脉更强；（2）小动脉在某些浓度下对PAF有双相反应；（3）PAF诱导的血管收缩而非扩张是受体介导的；（4）一氧化氮减弱气管静脉收缩，并可能在PAF作用下导致小动脉扩张；（5）内源性NO释放似乎对气管小动脉基础张力的调节作用比对微静脉更强。
