Chronic heart rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice

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Abstract
Background and purpose: High resting heart rate is a predictor for total and cardiovascular mortality independent of other risk factors in patients with coronary artery disease. We tested the hypothesis that a reduction of resting heart rate with the cardiac pacemaker If current inhibitor ivabradine prevents the endothelial dysfunction associated with dyslipidaemia. Experimental approach: Three‐month‐old dyslipidaemic (DL) male mice expressing the human ApoB‐100 were assigned or not (DL, n=16), to treatment for 3 months with ivabradine (10 mg kg−1 d−1, n=17). Wild‐type C57Bl/6 mice (WT, n=15) were used as controls. Heart rate was measured at 3, 4.5 and 6 months. Dilatation to acetylcholine (ACh) of isolated cerebral and renal arteries was investigated at 6 months. Key results: Heart rate remained stable in anaesthetized WT mice, increased (25%, PPPPPPBritish Journal of Pharmacology (2008) 154, 749–757; doi:fn2; published online 14 April 2008