EARLY GENES INDUCTION IN SPONTANEOUSLY HYPERTENSIVE RATS LEFT-VENTRICLE WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS BUT NOT HYDRALAZINE

Spontaneously hypertensive rats were given an angiotensin-converting e nzyme (ACE) inhibitor (benazepril or quinapril) or hydralazine and wer e left for up to 6 hr. To examine whether administration of antihypert ensive agents affects expression of immediate early genes in left vent ricular myocardium, groups of rats were sacrificed at 1, 3, and 6 hr a fter dosing; total RNA was extracted from left ventricular tissue and analyzed by blot hybridization technique using labeled probes for c-my c, c-fos, and GAPDH mRNA, All three antihypertensive agents reduced pr essure similarly, and treatment with the two ACE inhibitors increased c-fos and c-myc mRMA expression in left ventriculum. By contrast, hydr alazine did not increase steady-state mRNA expression of either proto- oncogene. Thus, in parallel with the pressure fall, acute administrati on of the ACE inhibitors induced expression of c-fos and c-myc mRNAs i n the left ventricle. since the equidepressor dose of hydralazine did not affect expression of these proto-oncogenes, this effect of ACE inh ibitors is independent of their hemodynamic action.