Exercise hyperaemia in the heart: the search for the dilator mechanism.

Coronary blood flow is tightly coupled to myocardial oxygen consumption to maintain a consistently high level of myocardial oxygen extraction over a wide range of physical activity. This tight coupling has been proposed to depend on periarteriolar oxygen tension, signals released from cardiomyocytes (adenosine acting on K(ATP) channels) and the endothelium (prostanoids(,) nitric oxide, endothelin) as well as neurohumoral influences (catecholamines, endothelin), but the contribution of each of these regulatory pathways, and their interactions, to exercise hyperaemia in the human heart are still incompletely understood. Thus, in the human heart, nitric oxide, prostanoids, adenosine and K(ATP) channels each contribute to resting tone, but evidence for a critical contribution to exercise hyperaemia is lacking. In dogs K(ATP) channel activation together with adenosine and nitric oxide contribute to exercise hyperaemia in a non-linear redundant fashion. In contrast, in swine nitric oxide, adenosine and K(ATP) channels contribute to resting coronary resistance vessel tone control in a linear additive manner, but are not mandatory for exercise hyperaemia in the heart. Rather, exercise hyperaemia in swine appears to involve K(Ca) channel opening that is mediated, at least in part, by exercise-induced beta-adrenergic activation, possibly in conjunction with exercise-induced blunting of an endothelin-mediated vasoconstrictor influence. In view of these remarkable species differences in coronary vasomotor control during exercise, future studies are required to determine whether exercise hyperaemia in humans follows a canine or porcine control design.