With regard to K+ , stimuli such as hypoxia, electrical stimulation of the brain, and seizures elicit rapid increases in cerebral blood flow, and they are associated with increases in perivascular K+ . The increments in K+ are similar to those that produce pial arteriolar dilation when K+ is applied topically to these vessels. When extracellular K+ exceeds 15 mEq/L, smooth muscle cells depolarize, and Ca++ entry is increased to cause contraction and vasoconstriction. Thus the extracellular [K+] has a dual effect on smooth muscle function that is derived from its actions on Na+/K+-ATPase, K+ conductance, and the K+ concentration gradient.
The cerebral vessels are also regulated by CO2. Increases in arterial blood CO2 tension (PaCO2) elicit marked cerebral vasodilation; for example, inhalation of 7% CO2 increases cerebral blood flow twofold. Conversely, decreases in PaCO2, caused by hyperventilation, diminish cerebral blood flow. CO2 evokes changes in arteriolar resistance by altering perivascular pH. When PaCO2 and the HCO3 − concentration are independently changed, pial vessel diameter and blood flow are inversely related to pH, regardless of the level of PaCO2 or [HCO3 −]. Acidosis initiates a marked vasodilation of brain arterioles. The vasodilation is mediated by a very localized release of Ca++ from the endoplasmic reticulum (Ca++ “sparks”). This local Ca++ signal activates large conductance BKCa channels; the ensuing hyperpolarization stabilizes the vascular smooth muscle cell and opposes vasoconstriction.
Elevationinintracranialpressure,causedbyabraintumor,resultsinanincreaseinsystemicbloodpressure.Thisresponse,calledCushing’s phenomenon, isevokedbyischemicstimulationofvasomotorregionsinthemedulla.Cushing’sphenomenonhelpsmaintaincerebralbloodflowinconditionssuchasexpandingintracranialtumors.
Carbon dioxide diffuses into vascular smooth muscle from brain tissue or from the lumen of blood vessels, whereas H+ in blood is prevented from reaching arteriolar smooth muscle by the blood-brain barrier. Hence, cerebral vessels dilate when the [H+] of cerebrospinal fluid is increased, but these vessels dilate only minimally in response to an increase in the [H+] of arterial blood. Chemical regulation of cerebral blood flow by PaCO2 is impaired in humans with endothelial dysfunction (e.g., diabetes, hypertension); the relative roles of H+ and NO in response to changes of PaCO2 are not clear.
Potassium concentration also affects cerebral blood flow. Hypoxia, electrical stimulation of the brain, and seizures elicit rapid increases in cerebral blood flow and in perivascular [K+]. The increases in [K+] are similar in magnitude to those that produce pial arteriolar dilation when K+ is applied topically to these vessels. However, the increase in [K+] is not sustained throughout the period of cerebral stimulation. Thus only the initial increase in cerebral blood flow can be attributed to the release of K+ .