Susic D, Aristizabal D J, Prakash O, Nunez E, Frohlich E D
Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
Proc Soc Exp Biol Med. 1995 Dec;210(3):266-9. doi: 10.3181/00379727-210-43948.
Spontaneously hypertensive rats were given an angiotensin-converting enzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and were left for up to 6 hr. To examine whether administration of antihypertensive agents affects expression of immediate early genes in left ventricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr after dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-myc, c-fos, and GAPDH mRNA. All three antihypertensive agents reduced pressure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRNA expression in left ventriculum. By contrast, hydralazine did not increase steady-state mRNA expression of either proto-oncogene. Thus, in parallel with the pressure fall, acute administration of the ACE inhibitors induced expression of c-fos and c-myc mRNAs in the left ventricle. Since the equidepressor dose of hydralazine did not affect expression of these proto-oncogenes, this effect of ACE inhibitors is independent of their hemodynamic action.
给自发性高血压大鼠服用一种血管紧张素转换酶（ACE）抑制剂（贝那普利或喹那普利）或肼屈嗪，并持续观察长达6小时。为了研究抗高血压药物的给药是否会影响左心室心肌中即早基因的表达，在给药后1、3和6小时处死几组大鼠；从左心室组织中提取总RNA，并使用针对c-myc、c-fos和GAPDH mRNA的标记探针通过印迹杂交技术进行分析。所有三种抗高血压药物降低血压的效果相似，两种ACE抑制剂的治疗增加了左心室中c-fos和c-myc mRNA的表达。相比之下，肼屈嗪并未增加这两种原癌基因的稳态mRNA表达。因此，与血压下降同时，急性给予ACE抑制剂可诱导左心室中c-fos和c-myc mRNA的表达。由于肼屈嗪的等效降压剂量不影响这些原癌基因的表达，ACE抑制剂的这种作用与其血流动力学作用无关。
