title: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00154024.
authors.affiliation: Clinical Research Center Hannover & Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany; Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schindler
authors.affiliation: Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Guenther
authors.affiliation: Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany.
authors.forename: Cosima
authors.initials: C
authors.lastname: Hermann
authors.affiliation: Departments of Surgery, Internal Medicine - Nephrology, Physiology-Pharmacology; Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.affiliation: Clinical Research Center Hannover & Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schroeder
authors.affiliation: Clinical Research Center Hannover & Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Haufe
authors.affiliation: Clinical Research Center Hannover & Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
authors.affiliation: Institute of Clinical Pharmacology, Medical Faculty, Technical University Dresden, Dresden, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Kirch
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000502:physiology*; D004311:Double-Blind Method; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D014661:Vasoconstriction / Q000502:physiology*; D014680:Veins / Q000503:physiopathology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000804:Angiotensin II