Regulation of Coronary Blood Flow During Exercise

Abstract

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases e...

Deleterious Effects of Cold Air Inhalation on Coronary Physiological Indices in Patients With Obstructive Coronary Artery Disease

“…While vasodilatation of small arteries and arterioles may prevail over α‐1‐adrenoceptor‐mediated vasoconstriction in patients with unobstructed coronary arteries,33 patients with obstructive coronary stenoses are reliant on constant metabolic vasodilation of arterioles,9 evidenced by significantly lower minimal MVR at rest. These arterioles are therefore unable to compensate for vasoconstriction of small arteries in response to cold, resulting in increased MVR.…”

“…One of the triggering events may be the deleterious effect of cold air on coronary blood flow 5, 8. Patients with obstructive coronary stenoses have less coronary vasodilator reserve and maybe particularly vulnerable to such deleterious effects 9. Changes in coronary blood flow are principally mediated by changes in coronary microvascular resistance (MVR).…”

Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts

“…Coronary flow is tightly regulated to maintain a consistently high level of myocardial oxygen extraction over a wide range of myocardial demands [1][2][3]. This tight regulation is dependent on numerous vasoconstrictor and vasodilator influences, exerted by the autonomic nervous system, endothelium, and myocardium [3][4][5][6].…”

“…This tight regulation is dependent on numerous vasoconstrictor and vasodilator influences, exerted by the autonomic nervous system, endothelium, and myocardium [3][4][5][6]. Adenosine, a well-known locally released metabolite, has been postulated as one of the important agents responsible for coronary vascular tone regulation in various conditions [3,5,[7][8][9], among which adenosine has also been thought to regulate resting coronary flow [10,11].…”

“…Adenosine, a well-known locally released metabolite, has been postulated as one of the important agents responsible for coronary vascular tone regulation in various conditions [3,5,[7][8][9], among which adenosine has also been thought to regulate resting coronary flow [10,11]. However, the role of adenosine in regulating resting coronary flow remains controversial [3]. This discrepancy may be due to different animal models, differences in species, and/or different agonists and antagonists used in these studies.…”