Alpha-Adrenergic Coronary Vasoconstriction in Humans

I read with interest the study of Jensen et al. (1) and the accompanying editorial (2). Jensen et al. demonstrated the abundance of the α_1D-adrenoceptor subtype on the mRNA and by radioligand binding on the protein level in epicardial coronary arteries of explanted healthy and diseased human hearts. This information is novel and potentially important for the development of more specific α-adrenoceptor blockers to treat hypertension and/or prostate hyperplasia. The accompanying editorial correctly emphasizes the importance of studies in human rather than animal tissue. The original study and the editorial, however, do not acknowledge the limitations of the in vitro nature of the study. Specifically, no information on the morphological and/or functional status of the analyzed coronary arterial segment with respect to its underlying atherosclerosis is provided. In fact, mRNA and radioligand binding of an adrenoceptor in vitro are one thing, but their functional contribution to coronary blood flow in vivo is a different thing. The original study and the editorial do not acknowledge that: 1) coronary blood flow in humans is tightly regulated by redundant mechanisms such that α-adrenergic vasoconstriction has little impact under physiological conditions; and 2) microvascular α₂-adrenoceptors are of greater importance than epicardial α₁-adrenoceptors, particularly in the presence of coronary stenoses (3). The functional importance of α₂-adrenergic coronary vasoconstriction was first demonstrated in dogs (4,5) and subsequently confirmed in humans in relevant clinical settings such as percutaneous coronary intervention (6–9). Thus, in the context of α-adrenergic coronary vasoconstriction, the “in vivo over in vitro” may outweigh the “human over animal” preference; studies in dogs are particularly suited because their coronary vascular α-adrenoceptor distribution is largely identical to that of humans (5,6). The original study and the editorial contrast human only to mouse and rat tissue. Clearly, studies in humans in vivo are preferable, notably with respect to polymorphisms (7) and also feasible with current imaging modalities (3).

• American College of Cardiology Foundation