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Statin therapy increases vascular sensitivity to angiotensin II in hypercholesterolaemic patients

Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK

John BC Dick

Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK

Allan D Struthers

Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK, a.d.struthers{at}dundee.ac.uk

Introduction 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

Cholesterol-lowering treatment with a statin was taken as a p value <0.05. Results Cholesterol-lowering treatment with alstatin 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 AT₁-receptors and AT₂-receptors.

Key Words: Hypercholesterolaemia • angiotensin • statins

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 3, 109-113 (2004)
DOI: 10.3317/jraas.2004.026


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