Experimental studies point to an interplay between hyper-cholesterolemia and hypertension, acting through the renin angiotensin system. In a crossover study design with 8 healthy subjects, the authors tested the hypothesis that statin treatment exerts renin angiotensin system-modulating effects in veins by down-regulation of AT₁-receptors, resulting in reduced Angiotensin II (Ang II)-induced venoconstriction and by increasing the pleiotropic Ang II-metabolite Ang-(1-7). Irbesartan was used as positive control. Ang II-induced venoconstriction was 49% ± 9% before and 64% ± 10% after 30 days of atorvastatin treatment compared to 50% ± 8% before and 15% ± 9% after irbesartan (P =.004). Plasma angiotensin levels significantly increased only after irbesartan treatment (Ang II: 35 ± 4 vs 329 ± 101 pg/mL [P =.02]; Ang-(1-7): 10 ± 3 vs 35 ± 6 pg/mL [P =.01]) compared to atorvastatin treatment (Ang II: 26 ± 5 vs 31 ± 4 pg/mL [P = ns]; Ang-(1-7): 9 ± 2 vs 11 ± 3 pg/mL [P = ns]). The data indicate that atorvastatin does not inhibit Ang II-induced venoconstriction in vivo and point toward a supportive role of Ang-(1-7) in contributing to the antihypertensive and beneficial vascular effects of irbesartan.