Adenosine has a significant impact on cerebral blood flow. It is released in the brain when there is ischemia, hypoxemia, hypotension, hypocapnia, electrical brain stimulation, or induced seizures. Topical application of adenosine causes dilation of the pial arterioles. Whenever there is a decrease in oxygen supply to the brain or an increase in oxygen requirements, adenosine quickly forms in cerebral tissue within 5 seconds. Unlike changes in pH or potassium concentration, adenosine levels remain elevated throughout the imbalance of oxygen. Adenosine released during cerebral ischemia becomes part of adenine nucleotides in cerebral tissue. These local factors, such as pH, potassium, and adenosine, work together to adjust cerebral blood flow according to the brain's metabolic activity. The cerebral circulation exhibits reactive hyperemia and excellent autoregulation when arterial blood pressure is between 60 and 160 mm Hg. A mean arterial pressure below 60 mm Hg reduces cerebral blood flow and can lead to syncope, while pressures above 160 mm Hg may cause increased permeability of the blood-brain barrier and cerebral edema. Autoregulation of cerebral blood flow is abolished by hypercapnia or any other potent vasodilator. It is likely mediated by a myogenic mechanism modulated by a metabolic component.

The gastrointestinal tract receives blood supply from the celiac, superior mesenteric, and inferior mesenteric arteries. The superior mesenteric artery carries more than 10% of the cardiac output. In the submucosa of the gastrointestinal tract, small mesenteric arteries form an extensive vascular network. These arterial branches penetrate the longitudinal and circular muscle layers of the tract and give rise to third and fourth-order arterioles. Some third-order arterioles in the submucosa supply the tips of the villi. Blood flow direction in the capillaries and venules of a villus is opposite to that in the main arteriole, creating a countercurrent exchange system. This system enables diffusion of oxygen from arterioles to venules. At low blood flow rates, a significant portion of oxygen may be shunted from arterioles to venules near the base of the villus, reducing oxygen supply to the mucosal cells at the tip of the villus. When intestinal blood flow is very low, oxygen shunting is so substantial that it leads to extensive necrosis of the intestinal villi.

Sympathetic control dominates the mesenteric circulation. Increased sympathetic activity, acting through α1-adrenergic receptors, causes constriction of mesenteric arterioles and capacitance vessels. β2-adrenergic receptors are also present, allowing vasodilation in response to the agonist isoproterenol. When aggressive behavior or artificial stimulation of the hypothalamic "defense" area occurs, pronounced vasoconstriction takes place in the mesenteric vascular bed. This redistribution of blood flow shifts it from the less essential intestinal circulation to the more crucial skeletal muscles, heart, and brain. Autoregulation of blood flow is less developed in the intestinal circulation compared to other vascular beds. Metabolic mechanisms primarily drive autoregulation, although a myogenic mechanism likely contributes as well.
Adenosine also has a major effect on cerebral blood flow. Adenosine levels in the brain increase in response to ischemia, hypoxemia, hypotension, hypocapnia, electrical stimulation of the brain, and induced seizures. Topically applied adenosine is a potent dilator of the pial arterioles. Any intervention that either reduces the O2 supply to the brain or increases the O2 requirements of the brain results in the rapid (within 5 seconds) formation of adenosine in cerebral tissue. Unlike the changes in pH or [K+], the adenosine concentration in the brain increases with initiation of the change in O2 supply, and it remains elevated throughout the period of O2 imbalance. The adenosine that is released into cerebrospinal fluid during cerebral ischemia becomes incorporated into adenine nucleotides in cerebral tissue. These local factors, including pH, K+, and adenosine, act in concert to adjust cerebral blood flow to the metabolic activity of the brain. The cerebral circulation displays reactive hyperemia
CHAPTER 17 Properties of the Vasculature and excellent autoregulation when arterial blood pressure is between 60 and 160 mm Hg. Mean arterial pressures below 60 mm Hg result in reduced cerebral blood flow and then syncope, whereas mean pressures above 160 mm Hg may lead to increased permeability of the blood-brain barrier and consequently to cerebral edema. Hypercapnia or any other potent vasodilator abolishes autoregulation of cerebral blood flow. Autoregulation of cerebral blood flow is probably mediated by a myogenic mechanism that is modulated by a metabolic component.
The gastrointestinal tract is supplied by the celiac, superior mesenteric, and inferior mesenteric arteries. The superior mesenteric artery carries more than 10% of the cardiac output. Small mesenteric arteries form an extensive vascular network in the submucosa of the gastrointestinal tract. The arterial branches penetrate the longitudinal and circular muscle layers of the tract, and they give rise to thirdand fourth-order arterioles. Some third-order arterioles in the submucosa supply the tips of the villi (
Fig. 17.42
The direction of blood flow in the capillaries and venules in a villus is opposite that in the main arteriole (see
Fig.
17.42 ). This arrangement is a countercurrent exchange system. Effective countercurrent exchange enables diffusion of O2 from arterioles to venules. At low blood flow rates, a substantial portion of the O2 may be shunted from arterioles to venules near the base of the villus. This reduces the O2 supply to the mucosal cells at the tip of the villus. When intestinal blood flow is very low, shunting of O2 is so great that extensive necrosis of the intestinal villi takes place.
Neural control of the mesenteric circulation is almost exclusively sympathetic. Increased sympathetic activity, through α1-adrenergic receptors, constricts the mesenteric arterioles and capacitance vessels. These receptors are preeminent in the mesenteric circulation. However, β2-adrenergic receptors are also present, and so the agonist isoproterenol causes vasodilation.
In response to aggressive behavior or to artificial stimulation of the hypothalamic “defense” area, pronounced vasoconstriction occurs in the mesenteric vascular bed. This vasoconstriction shifts blood flow from the less important intestinal circulation to the more crucial skeletal muscles, heart, and brain.
Autoregulation of blood flow is not as well developed in the intestinal circulation as in other vascular beds. The principal mechanism responsible for autoregulation is metabolic, although a myogenic mechanism probably also