Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis.

BACKGROUND AND PURPOSE: Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system. Here, we investigated in an atherosclerosis model, whether telmisartan (angiotensin receptor blocker) and ramipril (angiotensin converting enzyme inhibitor) are equivalent or the combination of both is superior in improving endothelial function in the aorta and the corpus cavernosum and in reducing atherosclerosis.

EXPERIMENTAL APPROACH: Wild-type (WT, C57/B6) and apolipoprotein-E-deficient (ApoE(-/-) ) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE(-/-) mice were supplemented with either telmisartan (20 mg·kg(-1) ·day(-1) ), ramipril (2.5 mg·kg(-1) ·day(-1) ) or the combination thereof.

KEY RESULTS: Systolic blood pressure significantly decreased in treatment groups (P < 0.001), with significantly smaller reduction under ramipril monotherapy (P < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and corpus cavernosum in organ bath chambers) was impaired in ApoE(-/-) mice compared to WT animals, which was improved by all three treatments to a comparable extent (P < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (P < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (P < 0.05) and free radical load (dihydroethidium-stain) (P < 0.05) were enhanced in untreated ApoE(-/-) mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by renin-angiotensin-aldosterone system blockade.

CONCLUSIONS AND IMPLICATIONS: Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE(-/-) via reduction of oxidative stress. Combination of both agents does not enhance beneficial effects significantly.