Carbocyclic thromboxane A2 enhances the angiotensin II-induced DNA synthesis in smooth muscle cells.
The present study describes the influence of carbocyclic thromboxane A2 on the proliferative effects of angiotensin II on vascular smooth muscle cells. Angiotensin II (10(-7) M) and carbocyclic thromboxane A2 (10(-6) M) per se caused an increase in [3H]thymidine incorporation and cell number. The exposure of cells to both agonists resulted in a 2.5-fold elevation of the angiotensin II dependent effect on DNA synthesis and a 1.6-fold increase in cell number. 2-Ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1 H-benzimidazole-7-carboxylic acid (CV-11974), the active metabolite of the specific non-peptide angiotensin AT1 receptor antagonist (+/-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1 H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1 H-benzimidazole-7-carboxylate (TCV-116, Candesartan) suppressed the effect of angiotensin II on cell growth as well as reduced the synergistic effect of carbocyclic thromboxane A2. Simultaneous cell stimulation with carbocyclic thromboxane A2 and angiotensin II for 30 min resulted in a 26 +/- 9% elevation of the angiotensin II-induced increase of c-fos mRNA (100%).
Sachinidis
A
A
Medizinische Universitäts-Poliklinik, Bonn, Germany.
el-Haschimi
K
K
Ko
Y
Y
Seul
C
C
Epping
P
P
Vetter
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D010975:Platelet Aggregation Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; C024587:thromboxane A2, carbocyclic; D000804:Angiotensin II; D013928:Thromboxane A2; D004247:DNA; C077793:candesartan cilexetil; C081643:candesartan