Robert E. Delong

Adenosine Deaminase Inhibitors Enhance Cerebral Anoxic Hyperemia in the Rat

Cerebral blood flow in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of flow over periods of several hours. The adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (1.0–100 μg/kg) and deoxycoformycin (0.1–1 μg/kg) potentiated the reactive hyperemia elicited by a brief (24-s) anoxic challenge. Basal flow rate was unaltered by EHNA administration and slightly enhanced by deoxycoformycin. The results are consistent with the hypothesis that adenosine plays a significant role in cerebral vascular regulation and suggest that low doses of these deaminase inhibitors may be useful in the treatment of cerebral vascular insufficiency.

Naloxone Enhances Cerebral Reactive Hyperemia in the Rat

Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of CBF over several hours. Morphine and the opiate antagonist, naloxone, were tested for their effects on the reactive hyperemia that follows a brief anoxic challenge. Morphine (5.0 mg/kg) significantly reduced the peak increase in flow during the hyperemia and, at both of the doses used (1.0 and 5.0 mg/kg), caused a small, nonsignificant increase in the duration of the reactive hyperemia. Naloxone (0.1 and 1.0 mg/kg) enhanced basal CBF rates and significantly prolonged the duration of the reactive hyperemia. These effects of naloxone may account for its beneficial effects in the treatment of cerebral ischemia.

The Effects of Nifedipine and Felodipine on Cerebral Blood Flow During Anoxic Episodes

Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of flow over periods of several hours. Brief periods of anoxia increase the rate of flow. The dihydropyridine calcium antagonists did not affect basal flow rate and depressed the increase in CBF elicited by anoxia. These findings may have significant implications for the therapeutic use of dihydropyridine calcium antagonists in brain ischaemia.

The role of adenosine in cerebral vascular regulation during reductions in perfusion pressure

The adenosine antagonist caffeine was used to test the hypothesis that endogenous adenosine contributes to the regulation of cerebral blood flow during acute reductions in mean arterial blood pressure. Caffeine, administered intraperitoneally in 20 and 40 mg kg−1 doses, failed to alter the autoregulatory flow responses to marked reductions in arterial blood pressure, showing that adenosine is not essential for cerebrovascular regulation during severe hypotension.

The effects of lidoflazine and flunarizine on cerebral reactive hyperemia

Cerebral blood flow in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of flow over periods of several hours. The bi-fluorophenyl-piperazine derivatives, lidoflazine and flunarizine, enhanced the reactive hyperemia elicited by a brief (30 s) anoxic challenge. They did not alter resting cerebral blood flow rates. Verapamil, a potent calcium slow channel blocker, decreased resting flow rates but did not alter the duration of the reactive hyperemia. As lidoflazine and flunarizine are potent inhibitors of adenosine uptake, whereas verapamil is not, the results are consistent with the hypothesis that adenosine plays a significant role in cerebral vascular autoregulation.

Indomethacin and ibuprofen enhance anoxia-induced hyperemia in rat brain

Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of CBF over periods of several hours. Following intraperitoneal administration, two non-steroidal anti-inflammatory agents, indomethacin and ibuprofen (0.01 and 0.1 mg/kg) showed a tendency to increase resting CBF and the reactive hyperemia elicited by a brief (24 s) anoxic challenge was potentiated. A third agent, diclofenac sodium, was less effective, enhancing the hyperemic response only at the higher (0.1 mg/kg) dose level. The results indicate that indomethacin and ibuprofen may be of value in the treatment of diseases involving cerebrovascular insufficiency.

A purinergic component in the central actions of meprobamate

The anxiolytic propanediol carbamate, meprobamate, potentiates the depressant actions of adenosine on the firing of rat cerebral cortical neurons. Meprobamate inhibits the uptake of adenosine by rat cortical synaptosomes at concentrations within the therapeutic range. Potentiation of endogenously released adenosine can account for many of the central actions of meprobamate.