Beta-blockers and coronary flow reserve: the importance of a vasodilatory action

Coronary flow reserve (CFR) is the maximal increase in coronary blood flow (CBF) above its resting level for a given perfusion pressure when coronary vasculature is maximally dilated. Normally, hyperaemic CBF reaches values at least 2- to 3-fold greater than resting CBF. Reduction of CFR is mainly due to epicardial coronary artery stenosis or to coronary microvascular dysfunction. CFR can be determined by several techniques that measure CBF itself (e.g. positron emission tomography) or CBF velocities (Doppler methods) from which coronary flow velocity reserve is calculated. Hyperaemic coronary vasodilation can be obtained by pharmacological agents (e.g. adenosine and dipyridamole), but also by the cold pressure test. Long-term antihypertensive treatment induces significant improvement of CFR, which is parallel to the regression of left ventricular (LV) hypertrophy. First- and second-generation beta-adrenergic receptor antagonists (beta-blockers) have shown contradictory influences on CFR. This can be explained by the interaction of the effects on CBF at rest, generally reduced by these drugs, and after hyperaemia, when minimal coronary resistance appears to be either increased or reduced. Third-generation beta-blockers (e.g. carvedilol and nebivolol), which have vasodilating capacity, improve hyperaemic CBF. This occurs as a result of a reduction in minimal resistance, which can be attributed to alpha-adrenergic blockade and/or to a nitric oxide-mediated effect. This improvement is clearly beneficial in patients with coronary artery disease and indicates an improved coronary microvascular function. Changes of CFR due to vasodilating beta-blockers improve microvascular angina pectoris or silent ischaemia in patients without epicardial artery stenosis, and are also helpful in predicting the response or the further improvement of LV function to treatment.