Lee R M, Tsoporis J, Wang R R
Smooth Muscle Research Programme, McMaster University, Hamilton, Ont., Canada.
Can J Physiol Pharmacol. 1992 Sep;70(9):1261-70. doi: 10.1139/y92-175.
Chronic treatment of spontaneously hypertensive rats (SHR) and Kyoto-Wistar normotensive rats (WKY) with nadolol was carried out from gestation until 28 weeks of age. Nadolol treatment caused some lowering of blood pressure but did not prevent the development of hypertension or cardiac hypertrophy in the SHR, in spite of significant beta-blockade. The lumen of large mesenteric arteries from control SHR was smaller than from WKY, and nadolol treatment increased the lumen size in the SHR. An increased number of smooth muscle cell layers present in the control SHR as compared with WKY was reduced slightly by nadolol treatment. However, the changes produced by nadolol did not reach the levels of control and treated WKY. In the aorta, the incidence of polyploid smooth muscle cells was higher in the SHR than the WKY in the control group. Nadolol treatment reduced the percentage of polyploid cells in both SHR and WKY, so that the difference between these two groups of animals was eliminated in the treated groups. The tissue level of norepinephrine in the plasma, heart, mesenteric arteries, and adrenal glands in the SHR and WKY was not affected by the treatment. We suggest that the ineffectiveness of nadolol in preventing hypertension development may be due to its lack of effect in preventing primary changes in the resistance arteries, and that the development of polyploidy of smooth muscle cells may be mediated by beta-receptors.
从妊娠至28周龄，用纳多洛尔对自发性高血压大鼠（SHR）和京都-威斯塔正常血压大鼠（WKY）进行长期治疗。尽管纳多洛尔有显著的β受体阻滞作用，但它使血压有所降低，但并未阻止SHR发生高血压或心脏肥大。对照SHR的肠系膜大动脉管腔比WKY的小，纳多洛尔治疗使SHR的管腔大小增加。与WKY相比，对照SHR中存在的平滑肌细胞层数增加，纳多洛尔治疗使其略有减少。然而，纳多洛尔产生的变化未达到对照和治疗WKY的水平。在主动脉中，对照组SHR中多倍体平滑肌细胞的发生率高于WKY。纳多洛尔治疗降低了SHR和WKY中多倍体细胞的百分比，因此在治疗组中消除了这两组动物之间的差异。SHR和WKY的血浆、心脏、肠系膜动脉和肾上腺中去甲肾上腺素的组织水平不受治疗影响。我们认为，纳多洛尔在预防高血压发展方面无效可能是由于其在预防阻力动脉的原发性变化方面缺乏作用，并且平滑肌细胞多倍体的发展可能由β受体介导。
