Review article
The paradox of α-adrenergic coronary vasoconstriction revisited

https://doi.org/10.1016/j.yjmcc.2011.03.007Get rights and content

Abstract

Activation of coronary vascular α-adrenoceptors results in vasoconstriction which competes with metabolic vasodilation during sympathetic activation. Epicardial conduit vessel constriction is largely mediated by α1-adrenoceptors; the constriction of the resistive microcirculation largely by α2-adrenoceptors, but also by α1-adrenoceptors. There is no firm evidence that α-adrenergic coronary vasoconstriction exerts a beneficial effect on transmural blood flow distribution. In fact, α-blockade in anesthetized and conscious dogs improves blood flow to all transmural layers, during normoperfusion and hypoperfusion. Also, in patients with coronary artery disease, blockade of α1- and α2-adrenoceptors improves coronary blood flow, myocardial function and metabolism.

Research highlights

► The coronary circulation has α1– and α2-adrenoceptors. ► α-Adrenergic coronary vasoconstriction competes with metabolic and endothelium-dependent vasodilation. ► α-Adrenoceptor blockade improves blood flow to all transmural layers. ► The dog coronary circulation is a good model for the human coronary circulation. ► Adrenoceptor blockade improves blood coronary blood flow and attenuates ischemia in patients.

Introduction

Sympathetic activation during excitement, exercise and other situations of stress (e.g. pain [1] or atrial fibrillation [2], [3]) results in β-adrenoceptor mediated increases in heart rate and ventricular function. The resulting increase in myocardial oxygen consumption is matched by an increased coronary blood flow through metabolic coronary vasodilation [4], [5], [6]. The activation of coronary vascular α-adrenoceptors by neuronal and humoral catecholamines induces vasoconstriction [7], [8], [9]. Such α-adrenergic coronary vasoconstriction in a situation of increased myocardial oxygen requirements appears paradox [8]. Indeed, in a normal coronary circulation, metabolic vasodilation prevails, but α-adrenergic vasoconstriction nevertheless competes and limits the increase in coronary blood flow [10], [11] such that myocardial oxygen extraction must also increase to match the increased myocardial oxygen requirements [6]. However, as compared to the cutaneous or skeletal muscle circulation, α-adrenergic vasoconstriction in the coronary circulation is only modest [12].

The apparent paradox of α-adrenergic coronary vasoconstriction has raised two fundamental questions: 1) Is there a physiological function for such α-adrenergic coronary vasoconstriction?, and 2) Does α-adrenergic coronary vasoconstriction contribute to the precipitation of ischemia in the presence of coronary stenoses and a limited coronary reserve?

Section snippets

Vascular α-adrenoceptor subtypes and pharmacological tool drugs

α-Adrenoceptors can be identified and classified on the basis of their binding characteristics and their molecular properties. However, the participation of α-adrenoceptors in the regulation of coronary vasomotor tone is largely determined from their activation by selective agonists and their inhibition by selective antagonists (Table 1) [9]. Usually, α-adrenoceptor agonists and antagonists are given after high-dose β-adrenoceptor blockade. β-Adrenoceptor blockade serves two purposes: a)

Magnitude of α-adrenergic coronary vasoconstriction and interaction with myocardial function and metabolism

Due to the competition with metabolic vasodilation, the extent of α-adrenergic coronary vasoconstriction is somewhat difficult to quantify. In the presence of β-blockade and at a coronary perfusion pressure well above the autoregulatory range, the intracoronary infusion of the selective α2-agonist xylometazoline increased coronary resistance by a maximum of 60% and the intracoronary infusion of the non-selective α-antagonist phentolamine decreased coronary resistance by a maximum of 60% in

α-Adrenergic vasoconstrictor impact on the transmural blood flow distribution

The proponents for a physiological function of α-adrenergic coronary vasoconstriction argue that in situations of sympathetic activation, such as exercise, excitement, pain etc., the increased heart rate (and reduced diastolic duration) as well as the increased left ventricular pressure tend to limit increases in blood flow to the inner myocardial layers, and that α-adrenergic coronary vasoconstriction tends to counteract the enhanced extravascular compression, thus – in a teleological sense –

α-Adrenergic coronary vasoconstriction during myocardial ischemia — experimental

The traditional view that myocardial ischemia is such a powerful stimulus for coronary vasodilation that vasoconstrictor mechanisms are no longer operative is certainly not correct. In fact, a number of studies have clearly demonstrated persistent vasoconstrictor tone in ischemic myocardium [55], [56], [57], [58]. Also, α-adrenergic coronary vasoconstriction is still operative in ischemic myocardium. In fact, when perfusion pressure was lowered below the autoregulatory range, α-adrenergic

α-Adrenergic coronary vasoconstriction during myocardial ischemia — clinical

The available small-scale, proof-of-concept studies provide reasonable evidence for a favorable effect of α-blockade in patients with coronary artery disease [24]. As in dogs, the human coronary circulation processes α1-adrenoceptors, predominantly in epicardial conduit vessels [25], [65], [66], and α2-adrenoceptors, predominantly in the resistive microcirculation [25]. Endothelial dysfunction predisposes to enhanced sympathetic vasoconstriction during the cold pressor test [67], and

Perspective

In conclusion, the idea of a beneficial effect of α-adrenergic coronary vasoconstriction on myocardial blood flow and function or metabolism is not thoroughly supported by the available data; there is no firm evidence to support better blood flow to the inner myocardial layers or better function/metabolism with α-adrenergic coronary vasoconstriction. Although under some specific experimental circumstances (such as maximal vasodilation and electrical cardiac sympathetic nerve stimulation) an

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