Abstract
In the present study, the effects of topically applied adenosine (ADO) and its stabile analogue 2-chloroadenosine (CADO) on cerebrocortical microcirculation and NAD/NADH redox state (oxidized/reduced nicotinamide adenine dinucleotide) were investigated. Vascular volume (CVV), mean transit time of blood flow (t m), blood flow (CBF), and NADH fluorescence of the cat brain cortex were measured through a cranial window with a microscope fluororeflectometer. The reference values of CVV,t m, and CBF, measured in the artificial cerebrospinal fluid (mock CSF) which superfused brain cortex, were regarded as 100%. Adenosine and 2-chloroadenosine, in the concentration range of 10−6–10−3 M, resulted in concentration-dependent increases in CBF and NAD reduction. 10−5 M adenosine and 2-chloroadenosine increased CBF by 49.6±5.6% and 80.4±10.3%, respectively. At a pharmacologically high concentration (10−3 M), ADO increased CBF by 164.6±13.5%, CADO by 333±44%. At the same time, 10−3 M ADO and CADO shifted the cortical NAD/NADH redox state by 7.9±0.4% and 12.4±0.7%, respectively toward a more reduced state. Our results, concerning the vasodilator potency of adenosine and 2-chloroadenosine, accord with available data in the literature. However, the pronounced NAD reduction obtained with these adenosine nucleosides suggests that, besides an action on vascular adenosine receptors, some other changes, such as increased substrate mobilization and possibly cAMP production, may contribute to the vasodilator effect of adenosine and 2-chloroadenosine.
Similar content being viewed by others
References
Astrup J, Heuser D, Lassen NA, Nilsson B, Norberg K, Biesjö BK (1978) Evidence against H+ and K+ as main factors for the control of cerebral blood flow: a microelectrode study. In: Cerebral Vascular Smooth Muscle (Ciba Foundation Symposium 56, new series), Amsterdam, Elsevier, pp 313–332
Berne RM, Rubio R, Curnish RR (1974) Release of adenosine from ischemic brain. Effect on cerebral vascular resistance and incorporation into cerebral adenine nucleotides. Circ Res 35:262–271
Betz E, Csornai M (1978) Action and interaction of perivascular H+, K+, and Ca2+ on pial arteries. Pflügers Arch 374:61–72
Dóra E, Zeuthen T, Silver IA, Chance B, Kovách AGB (1979) Effect of arterial hypoxia on the cerebrocortical redox state, vascular volume, oxygen tension, electrical activity and potassium ion concentration. Acta Physiol Hung 54:319–331
Dóra E (1984) A simple cranial window technique for optical monitoring of cerebrocortical microcirculation and NAD/NADH redox state. Effect of mitochondrial electron transport inhibitors and anoxic anoxia. J Neurochem 42:101–108
Dóra E (1985) Further studies on the reflectometric monitoring of cerebrocortical microcirculation. Importance of lactate anions in coupling between cerebral blood flow and metabolism. Acta Physiol Hung 66:199–211
Dóra E, Gyulai L, Kovách AGB (1984) Determinants of brain activation-induced cortical NAD/NADH responses in vivo. Brain Res 299:61–72
Dóra E, Koller A, Kovách AGB (1984) Effect of topical adenosine deaminase treatment on the functional hyperemic and hypoxic responses of cerebrocortical microcirculation. J Cereb Blood Flow Metabol 4:447–457
Eke A, Hutiray Gy, Kovách AGB (1979) Induced hemodilution detected by reflectometry for measuring microregional blood flow and blood volume in cat brain cortex. Am J Physiol 236:H759-H768
Emerson TE, Raymond RM (1981) Involvement of adenosine in cerebral hypoxic hyperemia in dog. Am J Physiol 241:H134-H138
Harbig K, Chance B, Kovách AGB, Reivich M (1976) In vivo measurement of pyridine nucleotide fluorescence from cat brain cortex. J Appl Physiol 41:480–488
Heistad DD, Marcus ML, Courley JK, Busija DW (1981) Effect of adenosine and dipyridamole on cerebral blood flow. Am J Physiol 240:H775-H780
Heuser D (1978) The significance of cortical extracellular H+, K+ and Ca2+ activities for regulation of local cerebral blood flow under conditions of enhanced neuronal activity. In: Cerebral Vascular Smooth Muscle (Ciba Foundation Symposium 56, new series), Amsterdam, Elsevier, pp 339–348
Howse DC, Coronna JJ, Duffy TE, Plum F (1974) Cerebral energy metabolism, pH, and blood flow during seizures in the cat. Am J Physiol 227:1444–1451
Huang M, Drummond GI (1979) Adenylate cyclase in cerebral microvessels: Action of guanine nucleotides, adenosine, and other agonists. Mol Pharmacol 16:462–472
Ibrahim MZM (1975) Glycogen and its related enzymes of metabolism in the central nervous system. Adv Anat Embryol Cell Biol 52:1–84
Kovách AGB, Dóra E, Szedlacsek S, Koller A (1983) Effect of the organic calcium antagonist D-600 on cerebrocortical vascular and redox responses evoked by adenosine, anoxia, and epilepsy. J Cereb Blood Flow Metabol 3:51–61
Kraig RP, Ferreira-Filho CR, Nicholson Ch (1983) Alkaline and acid transients in cerebellar microenvironment. J Neurophysiol 49:831–850
Kuschinsky W, Wahl M (1978) Local chemical and neurogenic regulation of cerebral vascular resistance. Physiol Rev 58:656–689
Leniger-Follert E, Hossmann KA (1979) Simultaneous measurement of microflow and evoked potentials in the somatomotor cortex of the cat brain during specific activation. Pflügers Arch 380:85–89
Leniger-Follert E, Danz C (1981) The role of extracellular potassium and hydrogen activities in the brain cortex for regulation of cerebral microcirculation in the cat during generalized seizures and specific sensory stimulation. In: Lübbers DW, Acker H, Buck RP, Eisenman G, Kessler M, Simon W (eds) Progress in Enzyme and Ion-Selective Electrodes. Berlin, Springer, pp 100–105
Leniger-Follert E (1984) Mechanisms of regulation of cerebral microflow during bicuculline-induced seizures in anaesthetized cats. J Cereb Blood Flow Metabol 4:150–165
Meier P, Zierler KL (1954) On the theory of the indicator-dilution method for measurement of blood flow and volume. J Appl Physiol 6:731–744
Nilsson B, Rehncrona S, Siesjö BK (1978) Coupling of cerebral metabolism and blood flow in epileptic seizures, hypoxia and hypoglycemia. In: Cerebral Vascular Smooth Muscle (Ciba Foundation Symposium 56, new series), Amsterdam, Elsevier, pp 199–214
Phelps ME, Grubb RL, Ter-Pogossian MM (1973) Correlation between\(Pa_{{\text{CO}}_{\text{2}} } \) and regional cerebral blood volume by X-ray fluorescence. J Appl Physiol 35:274–280
Rehncrona S, Siesjö BK, Westerberg E (1978) Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia. Acta Physiol Scand 104:453–463
Sattin A, Rall TW (1970) The effect of adenosine and adenine nucleotides on the cyclic adenosine 3′,5′-phosphate content of guinea pig cerebral cortex slices. Mol Pharmacol 6:13–23
Schrader J, Wahl M, Kuschinsky W, Kreutzberg GW (1980) Increase of adenosine content in cerebral cortex of the cat during bicuculline-induced seizure. Pflügers Arch 387:245–251
Siesjö BK (1978) Brain Energy Metabolism. New York, John Wiley and Sons
Smith AL, Neufeld GR, Ominsky AJ, Wollman H (1971) Effect of arterial CO2 tension on cerebral blood flow, mean transit time, and vascular volume. J Appl Physiol 31:701–707
Urbanics R, Leniger-Follert E, Lübbers DW (1978) Time course of changes of extracellular H+ and K+ activities during and after direct electrical stimulation of the brain cortex. Pflügers Arch 378:47–53
Ververken D, Van Veldhoven P, Proost C, Carton H, DeWulf H (1982) On the role of calcium ions in the regulation of glycogenolysis in mouse brain cortical slices. J Neurochem 38:1286–1295
Wahl M, Kuschinsky W (1976) The dilatatory action of adenosine on pial arteries of cats and its inhibition by theophylline. Pflügers Arch 362:55–59
Wahl M, Kuschinsky W (1977) Influence of H+ and K+ on adenosine induced dilatation at pial arteries of cats. Blood Vess 14:285–293
Wahl M, Kuschinsky W (1979) Unimportance of perivascular H+ and K+ activities for the adjustment of pial artery diameter during changes in arterial blood pressure in cats. Pflügers Arch 382:203–208
Winn HR, Rubio GR, Berne RM (1981) The role of adenosine in the regulation of cerebral blood flow. J Cereb Blood Flow Metabol 1:239–244
Winn RH, Rubio R, Berne RM (1981) Brain adenosine concentration during hypoxia in rats. Am J Physiol 241:H235-H242
Winn RH, Rubio R, Curnish RR, Berne RM (1981) Changes in regional cerebral blood flow (rCBF) caused by increases in CSF concentrations of adenosine and 2-chloroadenosine (CHL-ADO). J Cereb Blood Flow Metabol 1 (Suppl 1):S401-S402
Zetterström T, Vernet L, Ungerstedt U, Tossman U, Jonzon B, Fredholm BB (1982) Purine levels in the intact rat brain. Studies with an implanted perfused hollow fibre. Neurosci Lett 29:111–115
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dóra, E. Effect of adenosine and its stabile analogue 2-chloroadenosine on cerebrocortical microcirculation and NAD/NADH redox state. Pflugers Arch. 404, 208–213 (1985). https://doi.org/10.1007/BF00581241
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00581241