Analysis of vasoactivity of local pH, PCO2 and bicarbonate on pial vessels.

Abstract

SUMMARY The mechanism by which the local effect of CO 2 on pial arterioles is exerted was examined in anesthetized cats equipped with a cranial window for the direct observation of the microcirculation of the parietal cortex. The dilation of pial arterioles in response to application of artificial cerebrospinal fluid with low pH was the same whether or not the Pco 2 of the solution was maintained in the normal range or markedly increased. The constriction of pial arterioles in response to application of artificial cerebrospinal fluid with high pH was the same whether or not the Pco 2 of the solution was maintained in the normal range or markedly decreased. Finally, pial arterioles did not change their caliber in response to application of cerebrospinal fluid with unchanged pH but markedly increased or decreased Pco 2 , or bicarbonate ion concentration. These results show that the action of CO 2 on cerebral vessels is exerted via changes in extracellular fluid pH and that molecular CO 2 and bicarbonate ions do not have independent vasoactivity on these vessels.IT HAS BEEN demonstrated that local hypercapnic acidosis, induced by exposure of the surface of the brain to gaseous carbon dioxide or by application of acid solutions, produces dilation of cerebral vessels, in the absence of change in arterial blood Pco 2 .'"° Conversely, application of alkaline solutions produces vasoconstriction.1 ' M This local effect of CO 2 has been traditionally considered to be the major mechanism of its action on cerebral blood vessels and it is generally believed to be mediated through change in extracellular fluid pH. 7 It has never been demonstrated definitely, however, whether or not this local action of CO 2 is mediated exclusively through a change in local pH, or whether or not CO 2 has an additional action dependent on molecular CO 2 or on bicarbonate ion concentration and independent of changes in pH. Although the view that CO 2 is acting through a change in local pH overwhelmingly predominates, 8 the experiments supporting it, e.g., those based on application of acid or alkaline solutions to the surface of the brain, do not exclude effects dependent on molecular CO 2 or bicarbonate ions. Transient application of small amounts of acid or alkali under these circumstances is bound to alter both the pH and the CO a tension in the vicinity of the blood vessels, since body fluids contain bicarbonate ions which would buffer the change in pH. One cannot be certain that the ensuing changes in vessel caliber or blood flow are due to the change in pH or in Pco 2 or to both changes.The present experiments were designed to evaluate the independent actions of separate changes in pH and changes in CO 2 tension in the vicinity of the pial vessels. MethodsEighteen cats were anesthetized with intravenous sodium pentobarbital (30 mg/kg). The animals were paralyzed with intravenous decamethonium bromide (1 mg/kg) and ventilated with a positive pressure respirator connected to a tracheostomy tube. Expired CO 2 concentration was monitored conti...

Blockade of Nitric Oxide Synthesis in Rats Strongly Attenuates the CBF Response to Extracellular Acidosis

“…It is firmly established that the cerebrovascular response to hypercapnia or high aCSF P aco2 is not caused by a direct vasodilatory effect of CO2, but rather by changes in extracellular pH (Kontos et al, 1977). However, surprisingly little is known about the sequence of events from extracellular acidifica tion to smooth muscle relaxation (Busija and Hei stad, 1984).…”

The Contribution of Arterial Blood Gases in Cerebral Blood Flow Regulation and Fuel Utilization in Man at High Altitude

“…Altered arterial pH without changes in PaCO 2 does not effect CBF, 20 but extravascular application of acidic or basic solutions alters vessel tone. 21 The sensitivity to CO 2 thus appears to rely on diffusion of molecular CO 2 into the vascular wall where the resultant shift in extracellular pH drives changes in smooth muscle tone. 22 That CBF is a function of extravascular pH rather than arterial pH is further supported by the present data where CBF at HA was equivalent to SL despite chronic alkalosis, indicating CBF CO 2 sensitivity is reset over time at HA.…”

Cerebral Oxygenation in Awake Rats during Acclimation and Deacclimation to Hypoxia: AnIn VivoElectron Paramagnetic Resonance Study

“…An increase in the concentration of CO 2 increases CBF (Bereczki et al, 1993). The change in flow is likely to relate to the change in perivascular pH (Kontos et al, 1977;Apkon and Boron 1995). Perivascular acidosis will cause an increase in CBF.…”