Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

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

Role of Renin-Angiotensin System Components in Atherosclerosis: Focus on Ang-II, ACE2, and Ang-1–7

“…The role of statins on RAS components also have been observed in clinical trials as showed by Schindler et al (2014) that identified, for the first time, an increase of Ang-1-7 level in hypercholesterolemic subjects after atorvastatin treatment. Altogether, those responses suggest an important role of statins on RAS components, including a decrease in Ang-II and, apparently, an upregulation in the ACE2/Ang-1-7 axis.…”

Effects of Statins on Renin–Angiotensin System

“…For example, treatment of cholesterol-fed rabbits with atorvastatin increased the expression of ACE2 in the heart and kidney [ 84 ]. Treatment of rats with rosuvastatin after vascular balloon injury upregulated the expression of ACE2 and then the formation of Ang (1-7) [ 85 ]. In a clinical trial, it was shown that atorvastatin treatment of hypercholesterolemic subjects increased Ang (1-7)levels [ 86 ].…”