title: Statin therapy increases vascular sensitivity to angiotensin II in hypercholesterolaemic patients.
abstract: Cross-talk between various cardiovascular risk factors has been suggested by a number of studies. This study examines the interaction between hypercholesterolaemia and the renin-angiotensin system in vivo in man.
  
  
  METHODS
  We performed a randomised, placebo-controlled, double-blind crossover study on 40 hypercholesterolaemic patients, comparing cholesterol-lowering therapy with a statin for six months versus placebo. Brachial artery function was assessed by bilateral venous occlusion plethysmography using intra-arterial infusions of the endothelial-dependent vasoconstrictors, angiotensin I (Ang I) and angiotensin II (Ang II), to measure vascular angiotensin-converting enzyme (ACE) and Ang II receptor response respectively. The endothelial-independent vasoconstrictor, noradrenaline, was used as a control vasoconstrictor. Results were analysed by multiple analysis of variance and statistical significance was taken as a p value <0.05.
  
  
  RESULTS
  Cholesterol-lowering treatment with a statin significantly reduced the mean total cholesterol level to 5.71 mmol/L vs. 7.57 mmol/L on placebo (p<0.0001). Hypercholesterolaemia significantly increased the vasoconstriction response to noradrenaline (placebo versus statin treatment; p=0.046). In hypercholesterolaemia, there was a strong trend towards a reduction in the vasoconstriction response to Ang I (placebo versus statin treatment; p=0.089). In hypercholesterolaemia, the vasoconstriction response to Ang II was significantly reduced (placebo versus statin treatment; p=0.01).
  
  
  CONCLUSIONS
  Our in vivo results show that, unlike some other previous work, hypercholesterolaemia is associated with down-regulation of the vasoconstrictor response to Ang II and that statin therapy up-regulates the local vasoconstrictor response to Ang II. The possibility now arises that, in man, statins alter the balance between AT(1)-receptors and AT(2)-receptors.
authors.affiliation: Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
authors.forename: Justein Sn
authors.initials: JS
authors.lastname: Sim
authors.forename: John B C
authors.initials: JB
authors.lastname: Dick
authors.forename: Allan D
authors.initials: AD
authors.lastname: Struthers
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000803:Angiotensin I; D002784:Cholesterol; D009638:Norepinephrine