The cyclooxygenase inhibitors indomethacin and Rofecoxib reduce regional cerebral blood flow evoked by somatosensory stimulation in rats.
The present study was designed to investigate whether administration of indomethacin (IMC), a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and Rofecoxib, a highly selective COX-2 inhibitor, affect the regulation of regional cerebral blood flow response evoked by somatosensory activation (evoked rCBF). IMC and Rofecoxib were applied intravenously (6.25 and 3 mg/kg/hr, respectively). Somatosensory activation was induced by electrical hind paw stimuli of 0.2, 1, and 5 Hz (5-sec duration, 1.5 mA). The evoked rCBF was measured in alpha-chloralose anesthetized rats using laser-Doppler flowmetry. Before and after drug application, the evoked rCBF showed a frequency-dependent increase in the range of 0.2-5 Hz stimulation. IMC reduced significantly (about 50%-60%) evoked rCBF in response to all frequencies of hind paw stimulation (P< 0.05). Rofecoxib reduced significantly (about 50%) evoked rCBF in response to 1 and 5 Hz stimulation (P< 0.05), but did not affect evoked rCBF at 0.2 Hz. After IMC or Rofecoxib application, the normalized evoked rCBF curves peaked earlier as compared with that before their application (P< 0.05), although the rise time of 0.5 sec was nearly constant regardless of the stimulus frequency. The termination time of evoked rCBF curves was changed significantly after IMC application at 0.2 Hz stimulation (P< 0.05), but was not affected after Rofecoxib application. Neither COX inhibitor significantly affected the baseline level of CBF. The results suggest a participation of COX products in the regulation of evoked rCBF in response to somatosensory stimulation in the brain.
Bakalova
Rumiana
R
Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels, Akita 010-0874, Japan. r.bakalova-zheleva@aist.go.jp
Matsuura
Tetsuia
T
Kanno
Iwao
I
D000818:Animals; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation / Q000502:physiology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008565:Membrane Proteins; D009474:Neurons / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013003:Somatosensory Cortex / Q000098:blood supply*; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D007213:Indomethacin