Taddei S, Virdis A, Mattei P, Ghiadoni L, Fasolo C B, Sudano I, Salvetti A
I Clinica Medica, Universiy of Pisa, Italy.
Hypertension. 1997 Mar;29(3):736-43. doi: 10.1161/01.hyp.29.3.736.
We designed the present study to evaluate whether in normotensive subjects and hypertensive patients aging causes endothelial dysfunction by a defect in the L-arginine-nitric oxide pathway or production of cyclooxygenase-dependent vasoconstrictors. In 43 normotensive subjects and 47 essential hypertensive patients, we evaluated forearm blood flow (strain-gauge plethysmography) modifications evoked by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-dependent vasodilator, in the presence of saline, L-arginine (1 micromol/100 mL per minute), or indomethacin (50 microg/100 mL per minute), a cyclooxygenase inhibitor, and by sodium nitroprusside (1, 2, and 4 microg/100 mL per minute), an endothelium-independent vasodilator. Vasodilation to acetylcholine was lower (P<.01) in essential hypertensive patients than normotensive control subjects, and in both groups, it declined with advancing age. In normotensive subjects older than 30 years, L-arginine potentiated the response to acetylcholine in parallel with increasing age, whereas indomethacin increased the vasodilation to acetylcholine only in the oldest group (>60 years). In younger hypertensive patients (<30 years), L-arginine but not indomethacin potentiated the response to acetylcholine. In adult patients (31 to 45 years), L-arginine still potentiated the vasodilation to acetylcholine, and indomethacin began to show some effect. In the oldest patients (46 to 60 and >60 years), L-arginine was no longer effective, and indomethacin exerted a potentiating action that was positively related to advancing age. In normotensive and hypertensive humans, similar mechanisms, including dysfunction of the nitric oxide pathway and production of cyclooxygenase-dependent vasoconstrictors, cause age-related impairment of endothelium-dependent vasodilation, and only their earlier appearance characterizes hypertensive disease. Thus, the endothelial dysfunction that occurs in hypertension seems to represent an accelerated form of dysfunction that occurs in aging.
我们开展本研究，旨在评估在血压正常的受试者和高血压患者中，衰老是否通过L-精氨酸-一氧化氮途径缺陷或环氧化酶依赖性血管收缩剂的产生导致内皮功能障碍。在43名血压正常的受试者和47名原发性高血压患者中，我们评估了在生理盐水、L-精氨酸（1微摩尔/100毫升每分钟）或消炎痛（50微克/100毫升每分钟，一种环氧化酶抑制剂）存在的情况下，由肱动脉内注射乙酰胆碱（0.15、0.45、1.5、4.5和15微克/100毫升每分钟）（一种内皮依赖性血管扩张剂）引起的前臂血流量（应变片体积描记法）变化，以及由硝普钠（1、2和4微克/100毫升每分钟）（一种非内皮依赖性血管扩张剂）引起的前臂血流量变化。原发性高血压患者对乙酰胆碱的血管扩张反应低于血压正常的对照受试者（P<0.01），且在两组中，该反应均随年龄增长而下降。在30岁以上的血压正常受试者中，L-精氨酸随着年龄增长增强对乙酰胆碱的反应，而消炎痛仅在最年长组（>60岁）增加对乙酰胆碱的血管扩张作用。在较年轻的高血压患者（<30岁）中，L-精氨酸而非消炎痛增强对乙酰胆碱的反应。在成年患者（31至45岁）中，L-精氨酸仍增强对乙酰胆碱的血管扩张作用，且消炎痛开始显示出一定作用。在最年长的患者（46至60岁及>60岁）中，L-精氨酸不再有效，且消炎痛发挥的增强作用与年龄增长呈正相关。在血压正常和高血压人群中，包括一氧化氮途径功能障碍和环氧化酶依赖性血管收缩剂产生在内的类似机制导致与年龄相关的内皮依赖性血管扩张受损，且只有其更早出现才是高血压疾病的特征。因此，高血压中出现的内皮功能障碍似乎代表了衰老过程中发生的功能障碍的加速形式。
