EFFECT OF ANGIOTENSIN-II RECEPTOR BLOCKER ON ANGIOTENSIN-II STIMULATED DNA-SYNTHESIS OF CULTURED HUMAN AORTIC SMOOTH-MUSCLE CELLS

To examine the role of the renin-anggotensin system on human vascular smooth muscle cell (VSMC) replication, we studied the effect of DUP753, an angiotensin IE (ANG II) type 1 receptor antagonist, on ANG II stimulated tritiated-thymidine (H-3-Tdr) incorporation into cultured human aortic VSMC. ANG IL stimulated DNA synthesis of VSMC in a dose-dependent manner as estimated by H-3-Tdr incorporation (control; 2993 +/- 486 cpm, 10(-8)M; 3360 +/- 350 cpm, 10(-7)M; 3474 +/- 516 cpm, 10(-6)M; 4889 +/- 320 cpm, P < 0.01). The effects of ANG IE were: clearly inhibited by 10(-7)M DUP 753 (ANG II 10(-8)M; 3360 +/- 350 vs: 509 +/- 39 cpm, 10(-7)M; 3474 +/- 516 vs 661 +/- 36 cpm, 10(-6)M; 4889 +/- 320 vs 806 +/- 76 cpm, each P < 0.01). This receptor antagonist decreased the basal 3H-Tdr incorporation of VSMC from 2933 +/- 486 to 411 +/- 78 cpm (P < 0.01). Furthermore, DUP 753 decreased 10(-7)M ANG II-stimulated 3H-Tdr incorporation of VSMC in a dose-dependent manner (control; 2627 +/- 256 cpm, 10(-9)M; 2145 +/- 143 cpm, 10(-8)M; 1047 +/- 543 cpm, 10(-7)M 639 +/- 169 cpm,: 10(-6)M; 642 +/- 59 cpm, P < 0.01). These observations suggest that, in human VSMC, ANG II type I, receptors are important for the regulation of both stimulated and basal cell proliferation. It may therefore be worth while to examine the clinical usefulness of DUP 753 for preventing. abnormal VSMC growth.