Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
Am J Physiol Heart Circ Physiol. 2012 Apr 1;302(7):H1438-43. doi: 10.1152/ajpheart.01020.2011. Epub 2012 Jan 27.
The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with N(ω)-monomethyl-l-arginine (L-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to L-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as "positive" controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, L-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ∼30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study.
这项研究的目的是确定在高血压早期，一氧化氮（NO）是否会对血压产生抑制作用。NO 功能受损被认为是导致高血压的原因之一，但尚不清楚这是否是由于 NO 对血管张力的直接作用或对交感神经活动的间接调节。我们通过使用三甲噻酚来消除压力反射缓冲和 NO 对自主神经张力的调节，确定了一氧化氮合酶抑制（用 N（ω）-单甲基-L-精氨酸，L-NMMA）对血压的影响。在这种情况下，NO 对血管张力调节受损将反映为 L-NMMA 引起的升压反应减弱。我们共纳入了 66 名受试者（39 ± 1.3 岁，30 名女性），其中 20 名血压正常，20 名血压正常高值（血压在 120/80 至 140/90mmHg 之间），17 名高血压患者和 9 名吸烟者（包括作为 NO 功能受损的“阳性”对照）。三甲噻酚使高血压患者的血压正常化，表明交感神经张力增加是导致高血压的原因之一。相比之下，L-NMMA 使正常、血压正常高值和高血压患者的收缩压均显著升高（分别为 31 ± 2mmHg、32 ± 2mmHg 和 30 ± 3mmHg），而吸烟者的反应减弱（16 ± 5mmHg，P = 0.012）。我们的结果表明，交感神经活动在高血压中起作用。NO 通过约 30mmHg 的张力抑制血压，但我们没有发现 NO 对血管张力调节受损导致高血压早期发展的证据。如果 NO 缺乏导致高血压，那么很可能是通过其对自主神经系统的调节，而这在本研究中被排除在外。
