Rizzoni D, Porteri E, Piccoli A, Castellano M, Bettoni G, Muiesan M L, Pasini G, Guelfi D, Mulvany M J, Agabiti Rosei E
Department of Medical Sciences, University of Brescia, Italy.
Hypertension. 1998 Aug;32(2):305-10. doi: 10.1161/01.hyp.32.2.305.
We evaluated the effects on cardiovascular structure of the angiotensin-converting enzyme (ACE) inhibitor enalapril and of the angiotensin II receptor blocker losartan, administered either at hypotensive or nonhypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg x kg(-1) x d(-1)) enalapril, low-dose (0.5 mg x kg(-1) x d(-1)) losartan, high-dose (25 mg x kg(-1) x d(-1)) enalapril, or high-dose (15 mg x kg(-1) x d(-1)) losartan. Untreated WKY and SHR were also studied. Rats were killed at 13 weeks of age, and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness and lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbiased "disector" method. Systolic blood pressure was significantly reduced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (P<0.05). In the high-dose enalapril and losartan groups, there were similar reductions in relative left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of the structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodeling of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despite the smaller hypotensive effect.
我们评估了血管紧张素转换酶(ACE)抑制剂依那普利和血管紧张素II受体阻滞剂氯沙坦对自发性高血压大鼠(SHR)心血管结构的影响,这两种药物分别以降压剂量和非降压剂量给药。SHR从4周龄至12周龄接受低剂量(1mg·kg⁻¹·d⁻¹)依那普利、低剂量(0.5mg·kg⁻¹·d⁻¹)氯沙坦、高剂量(25mg·kg⁻¹·d⁻¹)依那普利或高剂量(15mg·kg⁻¹·d⁻¹)氯沙坦治疗。未治疗的WKY和SHR也进行了研究。大鼠在13周龄时处死,称量心脏重量。解剖肠系膜小动脉并安装在微血管张力测定仪上,以测定中膜厚度和管腔直径。在固定动脉中,使用无偏倚的“分割法”测量细胞体积、每段长度的细胞数量和细胞层数。两种药物的高剂量均显著降低收缩压,但依那普利的降压效果大于氯沙坦(P<0.05)。在高剂量依那普利和氯沙坦组中,相对左心室质量、中膜/管腔比值和阻力动脉细胞层数有相似程度的降低;然而,阻力动脉的细胞体积或每段长度的细胞数量没有差异。低剂量依那普利不影响收缩压或任何结构参数。结果表明,氯沙坦和依那普利的降压作用均与阻力动脉在细胞水平的向外重塑有关。尽管氯沙坦的降压作用较小,但其对阻力动脉结构的影响与依那普利相当。