Originally known for its vasoactive properties, angiotensin II is involved particularly in the regulation of blood pressure and cardiovascular homeostasis. Powerful mitogen, it is also involved in DNA damages inducing cellular and phenotypic changes occur in the initiation and tumor development, especially through its receptor AT1R.

Thus, the aim of this study was to evaluate the influence of a variation of blood pressure on tumor growth.

High blood pressure was induced in C57/BL6 mice by a chronic infusion of endothelin-1 (ET-1) in osmotic minipumps and one week later, mice were treated daily with the angiotensin receptor blocker candesartan or solvent. Tumor cells lung carcinoma (LL/2, 250000/mouse) were injected two weeks later and tumor growth was measured for 4 weeks.

The ET-1 induced hypertension (mean blood pressure 95mm Hg) induced a significant increase in tumor growth compared to NaCl treated mice (80mm Hg) while treatment by candesartan (70mm Hg) restored tumor volume to the level observed in normotensive animals. Antihypertensive treatment used had no effect on LL/2 cell proliferation in vitro but reduced tumor angiogenesis. Indeed, treatment with candesartan highlighted a significant decrease in the expression of PECAM-1 in murine tumors. Moreover, candesartan decreased the sprout formation in an ex vivo mouse aortic ring model in culture. Finally, candesartan reduced the migration and survival of endothelial cells (EaHY.926) in culture.Thus, candesartan could reduce tumor growth induced by hypertension ET-1-dependent, mainly by reducing angiogenesis. These results have to be confirmed by a non hypotensive dose of candesartan and the influence of the AT2R, induced by ARB treatments has to be explored.