Comparison of Inhibitory Effects of Irbesartan and Atorvastatin Treatment on the Renin Angiotensin System (RAS) in Veins: A Randomized Double‐Blind Crossover Trial in Healthy Subjects

Experimental studies point to an interplay between hypercholesterolemia 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.