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.
Schindler
Christoph
C
Institute of Clinical Pharmacology, Medical Faculty of the University of Technology, Fiedlerstrasse 27, D-01307 Dresden, Germany. christoph.schindler@tu-dresden.de
Brosnihan
K Bridget
KB
Ferrario
Carlos M
CM
Bramlage
Peter
P
Maywald
Ulf
U
Koch
Rainer
R
Oertel
Reinhard
R
Kirch
Wilhelm
W
D000328:Adult; D000803:Angiotensin I / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood / Q000494:pharmacology*; D000069059:Atorvastatin; D001713:Biphenyl Compounds / Q000097:blood / Q000494:pharmacology*; D003187:Compliance / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006538:Heptanoic Acids / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000494:pharmacology*; D000077405:Irbesartan; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D011758:Pyrroles / Q000097:blood / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D011758:Pyrroles; D013777:Tetrazoles; D000803:Angiotensin I; D000069059:Atorvastatin; C118790:angiotensin I (1-7); D000077405:Irbesartan