Role of Nitric Oxide in Regulating Cerebrocortical Oxygen Consumption and Blood Flow during Hypercapnia

Abstract

Summary: The effect of the nitric oxide (NO) synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) on the response of cerebrocortical oxygen consumption (CMR02) and blood flow (CBF) to two levels of hyper capnia (PaC02 -60 mm Hg and Pac02 -90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was cal culated using the Kety-Schmidt approach and CMR02 was calculated from the product of CBF and the arterio venous (superior sagittal sinus) difference for oxygen. L-NAME treatment did not have a significant effect onThe mechanism by which hypercapnia exerts its effect on cerebral blood flow is elusive. While part of the increase in cerebral blood flow is mediated through a local vascular reaction to hypercapnic ac idosis (Kontos et aI., 1977;Busija and Heistad, 1984), a number of central neuronal and peripheral neurohormonal factors may also play a role (Shalit et aI., 1967; MacKenzie et aI., 1976; Hemmingsen et aI., 1979; Berntman et aI., 1979; Siesjo et aI., 1980; Reddy et aI., 1986;Bryan, 1990; Dora et aI., 1992).Nitric oxide (NO) is a recently discovered mes senger molecule that mediates a wide variety of physiological and pathological effects in the cardio vascular, endocrinological, peripheral nervous, and central nervous systems (for reviews see Moncada et aI., 1991;Ignarro, 1991;and Synder, 1992). NO is 503either CMR02 or CBE under normocapnic conditions but inhibited the hypercapnic increase of CMR02 and the hy percapnic increase in CBF. These results suggest that NO plays a role in the response of CMR02 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hyper capnia is coupled to an increase in CMR02•

Cerebral metabolic rate in hypercapnia: Controversy continues

“…However, in another recently published study, Xu et al (2011) reported that mild hypercapnia resulted in a 13% suppression of CMRO 2 . This result is similar to (for example) previously published data in rhesus monkey (Kliefoth et al, 1979), but is opposite to reported increases in CMRO 2 in rats (Horvath et al, 1994). Some of this inconsistency in results between human and animal studies can be attributed to the different physiological conditions under which the experiments were performed.…”

Dynamics of Changes in Blood Flow, Volume, and Oxygenation: Implications for Dynamic Functional Magnetic Resonance Imaging Calibration

“…To obtain the calibrating factor (or constant), the approach applies hypercapnia perturbation with the assumption that CMRo 2 is unchanged (Yang and Krasney, 1995). However, other reports have shown significant increases in CMRo 2 during hypercapnia (Hovarth et al, 1994;Berntman et al, 1978;Hemmingsen et al, 1979), although these studies were performed under anesthesia. In addition, it is well known that there are astrocytic enzymes that can use CO 2 as an alternative energy source when it is present in abundance and hypercapnic levels that exceed the normal CO 2 arteriovenous difference, even by a few units of mm Hg, can be considered in excess of what the tissue needs because of the high solubility of CO 2 (Ursino et al, 1989a, b).…”

The Influence of Carbon Dioxide on Brain Activity and Metabolism in Conscious Humans

“…The results, however, were not consistent in the literature. A few studies (Barzilay et al, 1985;Kety and Schmidt, 1948;Novack et al, 1953) reported that CMRO 2 remains constant with hypercapnia, whereas other studies found a decrease (Kliefoth et al, 1979;Kogure et al, 1975;Sicard and Duong, 2005) or increase (Horvath et al, 1994;Jones et al, 2005;Yang and Krasney, 1995) in CMRO 2 . More recent findings in brain slices and anesthetized animals provided evidence at the cellular level that higher CO 2 partial pressure can have a profound effect on neural tissue including reducing pH, elevating adenosine concentration, and suppressing synaptic potentials (Dulla et al, 2005;Gourine et al, 2005;Zappe et al, 2008b).…”

“…In fact, the vascular effect of CO 2 may be a nuisance in the study of tissue. It is perhaps for these reasons that the exact influence of CO 2 inspiration on neural activity is not fully characterized to date (Horvath et al, 1994;Jones et al, 2005;Kety and Schmidt, 1948;Kliefoth et al, 1979).…”