Bank A J, Kubo S H, Rector T S, Heifetz S M, Williams R E
Cardiovascular Division, Minneapolis 55455.
Clin Pharmacol Ther. 1991 Sep;50(3):314-21. doi: 10.1038/clpt.1991.142.
To determine whether converting enzyme inhibitors could produce peripheral vasodilation through a local mechanism, we infused enalaprilat, 2 micrograms/min/dl forearm volume (FAV), into the brachial artery of normal subjects and measured changes in forearm blood flow (FBF) with strain-gauge plethysmography. Enalaprilat produced a peak increase in FBF of 2.82 +/- 0.54 ml/min/dl FAV (78% increase) at 1 minute (p less than 0.01 versus vehicle) and an increase of 1.11 +/- 0.28 ml/min/dl FAV at 4 minutes (p less than 0.05 versus vehicle). Blood pressure and plasma renin activity measured at the completion of infusion did not change. Intravenous enalaprilat infusion at the same dose in seven additional normal subjects did not increase FBF. Pretreatment of seven subjects with 75 mg oral indomethacin attenuated the peak response to enalaprilat (4.13 +/- 1.52 versus 0.58 +/- 0.32 ml/min/dl; p less than 0.05). We conclude that intra-arterial enalaprilat produces an increase in FBF in normal subjects. This peripheral vasodilation is caused by a local effect independent of circulating renin-angiotensin system inhibition. This response is attenuated by indomethacin, suggesting that prostaglandins contribute to the vasodilator response.
为了确定转换酶抑制剂是否能通过局部机制产生外周血管舒张作用，我们以2微克/分钟/分升前臂容积（FAV）的剂量将依那普利拉注入正常受试者的肱动脉，并使用应变片体积描记法测量前臂血流量（FBF）的变化。依那普利拉在1分钟时使FBF峰值增加2.82±0.54毫升/分钟/分升FAV（增加78%）（与赋形剂相比，p<0.01），在4分钟时增加1.11±0.28毫升/分钟/分升FAV（与赋形剂相比，p<0.05）。输注结束时测得的血压和血浆肾素活性未发生变化。在另外7名正常受试者中以相同剂量静脉输注依那普利拉并未增加FBF。7名受试者口服75毫克吲哚美辛预处理后，依那普利拉的峰值反应减弱（4.13±1.52与0.58±0.32毫升/分钟/分升；p<0.05）。我们得出结论，动脉内注射依那普利拉可使正常受试者的FBF增加。这种外周血管舒张是由一种独立于循环肾素-血管紧张素系统抑制的局部效应引起的。这种反应被吲哚美辛减弱，提示前列腺素参与了血管舒张反应。
