Abstract
Experimental studies suggested that statins attenuate vascular AT1 receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.Trial RegistrationClinicalTrials.gov NCT00154024
Highlights
Among lipid lowering drugs, statins are efficacious in ameliorating cardiovascular risk
The excessive pressor response to systemic angiotensin II infusion in hypercholesterolemic patients was normalized with statin treatment
Statin treatment in hypercholesterolemic men did not blunt venous constriction elicited by angiotensin II as suggested by in vitro results whereas AT1 receptor blockade profoundly attenuated the response
Summary
Statins are efficacious in ameliorating cardiovascular risk. Experimental studies suggested that statins could modify renin angiotensin system responses through AT1 receptor downregulation [1,2,3] and altered vascular signalling including interference with Rho protein prenylation [4]. Few studies have assessed renin angiotensin system-modulating statin actions in man. The excessive pressor response to systemic angiotensin II infusion in hypercholesterolemic patients was normalized with statin treatment. Statin treatment in hypercholesterolemic patients augmented rather than reduced forearm vasoconstriction to angiotensin II locally infused into the brachial artery [5]. We hypothesized that statin-induced downregulation of angiotensin II mediated venoconstriction may be unmasked in hypercholesterolemic subjects. Given the known interaction between renin angiotensin and nitric oxide systems, we tested for changes in endothelium dependent venodilation with statin treatment
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