Mayhan W G
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
J Lab Clin Med. 1999 Jan;133(1):48-54. doi: 10.1053/lc.1999.v133.a94238.
Although cigarette smoking and the components of cigarette smoke appear to alter nitric oxide synthase-dependent dilation of blood vessels, the effect of these substances on constrictor responses of resistance arterioles has not been examined. Thus the goal of this study was to examine the effect of a major component of cigarette smoke-that is, nicotine-on constrictor responses of cheek pouch arterioles. The diameter of cheek pouch arterioles (approximately 50 microm in diameter) was measured by using intravital microscopy. We examined the responses of arterioles to angiotensin II, arginine vasopressin, norepinephrine, and the thromboxane analog U-46619 before and after treatment with vehicle (saline solution), N(G)-monomethyl-L-arginine (L-NMMA; 1.0 micromol/L), or nicotine (2.0 microg/kg/min i.v. for 30 minutes followed by a maintenance dose of 0.35 microg/kg/min for 30 minutes). Topical application of angiotensin II (0.01 and 0.1 nmol/L), arginine vasopressin (1.0 and 10 pmol/L), norepinephrine (1.0 and 10 nmol/L), and U-46619 (0.01 and 0.1 nmol/L) produced marked reproducible constriction of cheek pouch arterioles in hamsters treated with vehicle. Topical application of L-NMMA potentiated constrictor responses of arterioles to the high dose of arginine vasopressin (28%+/-4% versus 36%+/-4%; P<.05) and to both doses of norepinephrine (14%+/-1% and 24%+/-2% versus 19%+/-1% and 31%+/-3%; P<.05). The infusion of nicotine did not alter responses to angiotensin II, arginine vasopressin, or U-46619 but modestly potentiated vasoconstriction in response to norepinephrine (12%+/-2% and 22%+/-2% versus 14%+/-2% and 26%+/-2%; P<.05). These findings suggest that the synthesis/release of nitric oxide may modulate constrictor responses of cheek pouch resistance arterioles to selected agonists. In addition, nicotine, at levels observed in smokers, may potentiate norepinephrine-induced vasoconstriction. We suggest that preservation/potentiation of vasoconstrictor responses may contribute to the pathogenesis of vascular abnormalities associated with cigarette smoking.
尽管吸烟及香烟烟雾成分似乎会改变一氧化氮合酶依赖性的血管舒张，但这些物质对阻力小动脉收缩反应的影响尚未得到研究。因此，本研究的目的是探讨香烟烟雾的一种主要成分——即尼古丁——对颊囊小动脉收缩反应的影响。采用活体显微镜测量颊囊小动脉（直径约50微米）的直径。在用溶媒（盐溶液）、N(G)-单甲基-L-精氨酸（L-NMMA；1.0微摩尔/升）或尼古丁（静脉注射2.0微克/千克/分钟，持续30分钟，随后维持剂量为0.35微克/千克/分钟，持续30分钟）处理前后，我们检测了小动脉对血管紧张素II、精氨酸加压素、去甲肾上腺素和血栓素类似物U-46619的反应。局部应用血管紧张素II（0.01和0.1纳摩尔/升）、精氨酸加压素（1.0和10皮摩尔/升）、去甲肾上腺素（1.0和10纳摩尔/升）和U-46619（0.01和0.1纳摩尔/升）可使接受溶媒处理的仓鼠颊囊小动脉产生明显的、可重复的收缩。局部应用L-NMMA可增强小动脉对高剂量精氨酸加压素（28%±4%对36%±4%；P<0.05）和两种剂量去甲肾上腺素（14%±1%和24%±2%对19%±1%和31%±3%；P<0.05）的收缩反应。输注尼古丁并未改变对血管紧张素II、精氨酸加压素或U-46619的反应，但适度增强了对去甲肾上腺素的血管收缩作用（12%±2%和22%±2%对14%±2%和26%±2%；P<0.05）。这些发现表明，一氧化氮的合成/释放可能调节颊囊阻力小动脉对特定激动剂的收缩反应。此外，吸烟者体内观察到的尼古丁水平可能会增强去甲肾上腺素诱导的血管收缩。我们认为，血管收缩反应的保留/增强可能有助于与吸烟相关的血管异常的发病机制。
