Soltis E E
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington.
J Pharmacol Exp Ther. 1993 Aug;266(2):642-6.
The current study was performed to investigate the effects of a 2-week treatment regimen with either hydralazine or the nonpeptide angiotensin II subtype 1 receptor antagonist losartan (both at 10 mg/kg daily s.c. injection) on blood pressure and vascular smooth muscle function and structure in male spontaneously hypertensive rats with established hypertension (24 weeks of age; systolic blood pressure = 174 +/- 7 mm Hg). Systolic blood pressure and body weight were recorded before and once weekly after initiation of treatment. Mean arterial pressure, heart rate and heart weight were determined and experiments were conducted to assess changes in vascular reactivity and arterial medial thickness in ring segments of aorta and tail artery at the end of the treatment period. Systolic blood pressure, as well as mean arterial pressure, were significantly decreased to normotensive levels in hypertensive rats after 2 weeks of either hydralazine or losartan treatment. No effect on heart rate was observed in response to either antihypertensive agent. Body weight was not affected in either of the treatment groups, but a significant decrease in artery ring weight, arterial medial thickness and heart weight was seen only in losartan-treated rats. Whereas no changes in vascular reactivity were seen in hypertensive rats receiving hydralazine, norepinephrine- and serotonin-induced contractions were attenuated and acetylcholine-induced relaxations were enhanced in the losartan-treated rats. These data demonstrate that, although short-term 2-week treatment with either hydralazine or losartan results in normalization of blood pressure, only losartan resulted in significant alterations in vascular function and structure in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在探讨为期2周的肼屈嗪或非肽类血管紧张素II 1型受体拮抗剂氯沙坦(均每日皮下注射10mg/kg)治疗方案对已患高血压(24周龄;收缩压=174±7mmHg)的雄性自发性高血压大鼠血压及血管平滑肌功能和结构的影响。在治疗开始前及开始后每周记录一次收缩压和体重。测定平均动脉压、心率和心脏重量,并在治疗期结束时进行实验,以评估主动脉和尾动脉环段血管反应性和动脉中膜厚度的变化。肼屈嗪或氯沙坦治疗2周后,高血压大鼠的收缩压以及平均动脉压均显著降至正常血压水平。两种降压药均未观察到对心率有影响。两个治疗组的体重均未受影响,但仅在氯沙坦治疗的大鼠中观察到动脉环重量、动脉中膜厚度和心脏重量显著降低。接受肼屈嗪治疗的高血压大鼠血管反应性未见变化,而氯沙坦治疗的大鼠中去甲肾上腺素和5-羟色胺诱导的收缩减弱,乙酰胆碱诱导的舒张增强。这些数据表明,虽然肼屈嗪或氯沙坦短期(2周)治疗均可使血压恢复正常,但只有氯沙坦能使自发性高血压大鼠的血管功能和结构发生显著改变。(摘要截断于250字)