Researchers are observing how coronary blood flow changes in response to progressive increases in the mean arterial blood pressure (see graph below).
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The mostly horizontal portion of the slope indicates a region where coronary blood flow is relatively insensitive to blood pressure changes. Within this zone of autoregulation, the metabolic demands of the myocardium are the main determinant of coronary blood flow. Which of the following endogenous factors is most responsible for controlling coronary blood flow within this range?
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The myocardium has the highest resting oxygen requirement of any tissue in the body, extracting >70% of available oxygen from the blood at baseline (compared to ~30% in most other tissues). As such, a significant increase in myocardial oxygen demand can only be met through a corresponding increase in coronary blood flow.
Coronary autoregulation is a process that maintains myocardial blood flow in settings of decreased coronary perfusion pressure (eg, hemorrhage, sepsis). Within the region of autoregulation (eg, 60-140 mm Hg), changes in coronary blood flow are driven primarily by myocardial oxygen demand. This is accomplished mostly by automated alterations in vascular resistance via the release of locally acting mediators, namely adenosine (released from cardiomyocytes as ATP is broken down for energy) and nitric oxide (synthesized by endothelial cells in response to chemical mediators and mechanical stress).
When myocardial perfusion pressure decreases, there is decreased oxygen delivery to the myocardium and less ATP is regenerated via oxidative metabolism, resulting in increased levels of adenosine. Myocardial hypoxia also triggers increased synthesis of nitric oxide. Increased levels of both adenosine and nitric oxide act on vascular smooth muscle to stimulate vasodilation, allowing for a relative increase in coronary blood flow at the new, lower perfusion pressure (ie, coronary blood flow is maintained). A similar process occurs when coronary perfusion pressure increases; decreased levels of adenosine and nitric oxide increase vascular resistance, causing coronary blood flow to remain relatively unchanged at the new, higher perfusion pressure.
(Choices A and E) Acetylcholine causes coronary vasodilation (via stimulation of endothelial nitric oxide release), and norepinephrine causes coronary vasoconstriction (via stimulation of alpha-1 receptors on vascular smooth muscle). However, compared to locally released mediators, autonomic nervous system stimulation has a relatively small effect on coronary blood flow.
(Choice B) Angiotensin II stimulates vasoconstriction of coronary arteries, but it is not involved in coronary autoregulation.
(Choice C) Histamine has variable vasoconstrictive and vasodilatory effects on coronary arteries depending on the type of histamine receptor triggered. However, histamine does not play a significant role in coronary autoregulation.
(Choice F) Serotonin primarily functions in the gastrointestinal tract and CNS. It may cause vasoconstriction of coronary arteries, evidenced by an association between 5HT1-receptor agonists (eg, sumatriptan) and coronary vasospasm. However, it is not significantly involved in coronary autoregulation.
Educational objective:
Coronary autoregulation allows coronary blood flow to be primarily driven by myocardial oxygen demand over a wide range of perfusion pressures (60-140 mm Hg). It is mostly accomplished by alterations in vascular resistance via release of adenosine and nitric oxide in response to myocardial hypoxia.