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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: UNLABELLED, METHODS, RESULTS. Meshes: Angiotensin I, Angiotensin II, Brachial Artery, Cholesterol, Cross-Over Studies, Double-Blind Method, Female, Forearm, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Male, Middle Aged, Norepinephrine, Regional Blood Flow, Vasoconstriction, Vasoconstrictor Agents.
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Does statin therapy increase vascular sensitivity to angiotensin II in hypercholesterolaemic patients? Context: 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. 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. 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).
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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. Final Decision: yes