Wilner K D, Ziegler M G
Am J Cardiol. 1987 May 29;59(14):82G-86G. doi: 10.1016/0002-9149(87)90163-9.
Doxazosin is a competitive inhibitor of norepinephrine at alpha 1 adrenoceptors on vascular smooth muscle, where it blocks vasoconstriction. Twenty-four patients with mild hypertension were treated with either doxazosin or placebo for 6 weeks. Supine and upright mean arterial pressures decreased by 9 and 12 mm Hg, respectively, in patients receiving doxazosin. This decrease was significantly more than the blood pressure change with placebo (p less than 0.05). Doxazosin therapy led to a small increase in weight (p less than 0.05). It was also associated with a statistically insignificant decrease in renal vascular resistance (568 dynes s/cm5) so that renal blood flow and creatinine clearance did not change. Doxazosin increased renin levels acutely and norepinephrine levels with 6-week treatment, but these changes were not significantly different from placebo. Norepinephrine clearance, measured after a 120-minute infusion of 3H norepinephrine, did not change. Heart rate increased acutely after doxazosin administration, but returned to baseline during 6-week therapy. Blood pressure, measured hourly for 14 hours after treatment, was consistently decreased in all patients. Doxazosin taken once daily lowers blood pressure without affecting renal blood flow or heart rate.
多沙唑嗪是去甲肾上腺素在血管平滑肌α1肾上腺素能受体上的竞争性抑制剂，它在该部位阻断血管收缩。24例轻度高血压患者接受多沙唑嗪或安慰剂治疗6周。接受多沙唑嗪治疗的患者仰卧位和直立位平均动脉压分别下降9和12 mmHg。这种下降显著大于安慰剂组的血压变化（p<0.05）。多沙唑嗪治疗导致体重略有增加（p<0.05）。它还与肾血管阻力有统计学意义不显著的下降（568达因·秒/厘米5）相关，因此肾血流量和肌酐清除率未发生变化。多沙唑嗪急性增加肾素水平，治疗6周后增加去甲肾上腺素水平，但这些变化与安慰剂组无显著差异。静脉输注3H去甲肾上腺素120分钟后测得的去甲肾上腺素清除率未发生变化。服用多沙唑嗪后心率急性增加，但在6周治疗期间恢复至基线水平。治疗后14小时每小时测量的血压在所有患者中持续下降。每日服用一次多沙唑嗪可降低血压，而不影响肾血流量或心率。
