Holt David C, Fedinec Alexander L, Vaughn Ashley N, Leffler Charles W
Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Exp Biol Med (Maywood). 2007 Dec;232(11):1465-9. doi: 10.3181/0705-BC-136.
In newborn pigs, carbon monoxide (CO) contributes to regulation of cerebrovascular circulation. Results from isolated adult cerebral arteries suggest CO may have less dilatory potential in mature animals. However, few data are available on the direct effects of CO on cerebrovascular circulation in vivo except for those from newborn pigs. Therefore, we tested the hypothesis that i) rat cerebral arterioles dilate to CO in vivo and ii) CO-induced cerebrovascular dilatory responses are age dependent in pigs. Also, we examined whether the permissive role of nitric oxide in CO-induced dilation observed in piglets is present in older pigs and rats. Experiments used anesthetized newborn, 7-week-old, and juvenile (3- to 4-month-old) pigs and 3- to 4-month-old rats with closed cranial windows and topical applications of CO and sodium nitroprusside (SNP). Dilations to SNP were not different at different ages in pigs or between pigs and rats. CO produced pial arteriolar dilations in all groups. Dilation to 10(-5) M CO was reduced in juvenile pigs as compared to newborn and 7-week-old pigs, and tended to less at 10(-6) M CO. Dilations of rat pial arterioles to all concentrations were less than those of newborn and 7-week-old pigs, but not different from those of juvenile pig pial arterioles. In newborn and 7-week-old pigs, l-nitro-arginine (LNA) inhibited the dilation to CO, an effect reversed by a constant background of SNP. In contrast, LNA did not reduce dilation to CO in juvenile pigs or rats. In conclusion, rat pial arterioles like those in piglets dilate to CO in vivo, but there are age and species differences with regard to reactivity and interaction with NO.
在新生猪中,一氧化碳(CO)有助于调节脑血管循环。来自分离的成年脑动脉的结果表明,CO在成熟动物中的扩张潜力可能较小。然而,除了新生猪的数据外,关于CO对体内脑血管循环的直接影响的资料很少。因此,我们检验了以下假设:i)大鼠脑微动脉在体内对CO有扩张反应;ii)CO诱导的脑血管扩张反应在猪中具有年龄依赖性。此外,我们研究了在仔猪中观察到的一氧化氮在CO诱导的扩张中的允许作用在成年猪和大鼠中是否存在。实验使用了麻醉的新生猪、7周龄猪和幼年(3至4月龄)猪以及3至4月龄大鼠,通过封闭的颅窗局部应用CO和硝普钠(SNP)。在不同年龄的猪之间或猪与大鼠之间,对SNP的扩张反应没有差异。CO使所有组的软脑膜微动脉扩张。与新生猪和7周龄猪相比,幼年猪对10⁻⁵ M CO的扩张反应减弱,对10⁻⁶ M CO的扩张反应也有减弱趋势。大鼠软脑膜微动脉对所有浓度CO的扩张反应均小于新生猪和7周龄猪,但与幼年猪软脑膜微动脉的扩张反应无差异。在新生猪和7周龄猪中,L-硝基精氨酸(LNA)抑制了对CO的扩张反应,这种作用可被持续的SNP背景逆转。相比之下,LNA在幼年猪或大鼠中并未降低对CO的扩张反应。总之,与仔猪一样,大鼠软脑膜微动脉在体内对CO有扩张反应,但在反应性以及与NO的相互作用方面存在年龄和物种差异。