Comparison of irbesartan versus atorvastatin therapy on angiotensin II (ANG II)‐induced venoconstriction and plasma levels of angiotensin‐(1–7)[ANG‐(1–7)] in healthy volunteers

Aim Experimental studies suggest interactions of statins with the renin‐angiotensin‐aldosterone‐system.[Ang‐(1–7)], the most pleiotropic metabolite of angiotensin II functions as a vasodilator by releasing prostaglandins and stimulating NO release. Methods In a randomized double blind double crossover study (n=8) we compared the effects of 30 days systemic therapy with irbesartan (150 mg; IRB) versus atorvastatin (20 mg; STAT) on Ang II‐ induced venoconstriction, endothelium dependent histamine and endothelium independent glyceroltrinitrate[GTN]‐induced dilation by the dorsal hand vein compliance method. Systemic treatments were separated by a 30 day washout period. Results Constant infusion of Ang II caused rapid venous desensitization that peaked after 8 minutes of infusion. Ang II‐induced constriction was 51±25% basal vein size (BVS) before and 36±28% BVS after 30 days of statin treatment (p=0.16) compared to 50±23% before vs 85±26% BVS after initiation of IRB treatment (p=0.012). There was no difference in histamine‐ and GTN‐induced dilation between treatments. Ang II‐levels were 26±13 before and 31±11 pg/mL after STAT (p=n.s.) and 35±12 before vs 329±285 pg/mL after IRB (p=0.02). Ang 1–7 levels were 9±6 before vs 11±9 pg/mL after STAT (p=n.s.) and 10±8 before vs 35±16 pg/mL after IRB (p=0.01). Conclusion A differential effect of STAT and IRB on venous compliance and plasma angiotensins in healthy volunteers suggests a venodilator action of[Ang‐(1–7)] following AT 1 ‐blockade. Clinical Pharmacology & Therapeutics (2005) 77 , P11–P11; doi: 10.1016/j.clpt.2004.11.045