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-angiotensin system on human vascular smooth muscle cell (VSMC) replication, we studied the effect of DUP 753, an angiotensin II (ANG II) type 1 receptor antagonist, on ANG II stimulated tritiated-thymidine (3H-Tdr) incorporation into cultured human aortic VSMC. ANG II stimulated DNA synthesis of VSMC in a dose-dependent manner as estimated by 3H-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 II 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 1 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.
Makita
S
S
Department of Internal Medicine II, Iwate Medical University, Morioka, Japan.
Nakamura
M
M
Yoshida
H
H
Hiramori
K
K
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D018450:Disease Progression; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D019808:Losartan; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D013268:Stimulation, Chemical; D013777:Tetrazoles / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014316:Tritium; D000804:Angiotensin II; D004247:DNA; D019808:Losartan; D013936:Thymidine