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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
Author(s) -
Schindler Christoph,
Brosnihan K. Bridget,
Ferrario Carlos M.,
Bramlage Peter,
Maywald Ulf,
Koch Rainer,
Oertel Reinhard,
Kirch Wilhelm
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006294280
Subject(s) - irbesartan , angiotensin ii , atorvastatin , renin–angiotensin system , medicine , crossover study , angiotensin ii receptor type 1 , aliskiren , endocrinology , pharmacology , valsartan , receptor , blood pressure , placebo , alternative medicine , pathology
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 AT 1 ‐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.