Davies R, Pickering T G, Morganti A, Bianchetti G, Morselli P L, Romankiewicz J, Laragh J H
Lancet. 1978 Feb 25;1(8061):407-10. doi: 10.1016/s0140-6736(78)91201-1.
Heart-rate, arterial pressure, and plasmarenin activity were determined in six normal subjects at rest and after an injection of 8 microgram isoprenaline with and without prior propranolol administered orally in a dose of 5 mg 8-hourly for a total of five doses. After propranolol, resting heart-rate, systolic pressure, and plasma-renin activity all fell significantly (P less than 0.05 to less than 0.001). When the isoprenaline-induced changes of heart-rate, diastolic pressure, and plasma renin activity without propranolol were compared to those with propranolol, these responses were greatly diminished (P less than 0.01 to less than 0.001). The percent blockade by propranolol of the isoprenaline-induced changes ranged from 65% for diastolic pressure to 77% for heart rate and 78% for plasma-renin activity. Propranolol levels determined by conventional fluorometry were below accurate detection limits, whereas those determined by gas-liquid chromatography ranged from 2.3 to 8.5 ng/ml. These findings, which demonstrate beta-blockade with low-dose propranolol, are not consistent with the existence of a postulated threshold for the hepatic "first-pass effect" in man, which is said to require saturation by single doses of 30 mg or more before propranolol enters the systemic circulation.
对6名正常受试者在静息状态下以及在注射8微克异丙肾上腺素后，分别测定心率、动脉压和血浆肾素活性，其中一半受试者在注射异丙肾上腺素前8小时口服5毫克普萘洛尔，共服用5剂。服用普萘洛尔后，静息心率、收缩压和血浆肾素活性均显著下降（P小于0.05至小于0.001）。将未服用普萘洛尔时异丙肾上腺素引起的心率、舒张压和血浆肾素活性变化与服用普萘洛尔后的变化进行比较，这些反应明显减弱（P小于0.01至小于0.001）。普萘洛尔对异丙肾上腺素引起的变化的阻断百分比范围为：舒张压65%，心率77%，血浆肾素活性78%。通过传统荧光法测定的普萘洛尔水平低于准确检测限，而通过气液色谱法测定的水平范围为2.3至8.5纳克/毫升。这些结果表明低剂量普萘洛尔具有β受体阻断作用，这与人类肝脏“首过效应”存在假定阈值的观点不一致，据说在普萘洛尔进入体循环之前，单次剂量需要30毫克或更多才能达到饱和。
