Teeuw A H, Leenen F H, Geyskes G G, Boer P
Clin Pharmacol Ther. 1979 Mar;25(3):294-302. doi: 10.1002/cpt1979253294.
The antihypertensive effect of atenolol, with and without chlorthalidone, on hypertension was assessed in an outpatient as well as in an inpatient study. In the outpatient study atenolol alone induced decreases in systolic and diastolic BP amounting to 20 and 15 mm Hg. Maximal response of BP and HR developed within a week at the lowest dose used (100 mg twice daily). Combined atenolol-chlorthalidone treatment decreased lying and standing systolic BP by 7 and 14 mm Hg more than atenolol alone, but diastolic BP was decreased little more. In the inpatient study the addition of atenolol to chlorthalidone therapy in a dose of 100 mg twice daily resulted in a maximal decrease in BP within 3 days. At this dose PRA was lowered only slightly. Larger doses did not lead to any significant further decrease in BP, whereas PRA fell progressively. Our results indicate that, in contrast to nonselective blockade, specific beta-1-adrenoceptor blockade by atenolol is capable of inducing a distinct antihypertensive effect, unrelated to suppression of PRA. The decrease in PRA after larger doses of atenolol was not accompanied by a further decrease in BP. Because diuretic-induced renin release plays a role in the maintenance of the BP, our findings suggest that at higher dosages a hypertensive effect of the beta blocker compensated for the hypotensive effect of the decrease in PRA.
在一项门诊和一项住院研究中，评估了阿替洛尔（单独使用及与氯噻酮联用）对高血压的降压效果。在门诊研究中，单独使用阿替洛尔可使收缩压和舒张压分别降低20 mmHg和15 mmHg。在使用的最低剂量（每日两次，每次100 mg）下，血压和心率在一周内出现最大反应。阿替洛尔与氯噻酮联合治疗比单独使用阿替洛尔使卧位和立位收缩压分别多降低7 mmHg和14 mmHg，但舒张压降低幅度稍小。在住院研究中，每日两次给予100 mg阿替洛尔并添加到氯噻酮治疗中，3天内血压出现最大降幅。在此剂量下，血浆肾素活性（PRA）仅略有降低。更大剂量并未导致血压进一步显著下降，而PRA则逐渐下降。我们的结果表明，与非选择性阻断不同，阿替洛尔对β1肾上腺素能受体的特异性阻断能够产生明显的降压作用，与PRA的抑制无关。大剂量阿替洛尔后PRA的降低并未伴随血压的进一步下降。由于利尿剂诱导的肾素释放对血压维持起作用，我们的研究结果表明，在较高剂量下，β受体阻滞剂的升压作用抵消了PRA降低的降压作用。
