Carbocyclic thromboxane A 2 enhances the angiotensin II-induced DNA synthesis in smooth muscle cells

Abstract

The present study describes the influence of carbocyclic thromboxane A 2 on the proliferative effects of angiotensin II on vascular smooth muscle cells. Angiotensin II (10 −7 M) and carbocyclic thromboxane A 2 (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-y1]methyl]-1 H-benzimidazole-7-carboxylic acid (CV-11974), the active metabolite of the specific non-peptide angiotensin AT 1 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 A 2. Simultaneous cell stimulation with carbocyclic thromboxane A 2 and angiotensin II for 30 min resulted in a 26 ± 9% elevation of the angiotensin II-induced increase of c-fos mRNA (100%).