Significance of an opiate mechanism in the adjustment of cerebrocortical oxygen consumption and blood flow during hypercapnic stress.
The role of adrenal medulla-derived enkephalins in the control of hypercapnic cerebrocortical blood flow (CBF) and oxygen consumption (CMRO2) was investigated in the ketamine anesthetized rat. Three experimental interventions were utilized: inhibition of opioid receptors with naloxone, decrease of adrenal enkephalin production with chronic adrenal medullectomy, and treatment of adrenal demedullated animals with the synthetic enkephalin analog, D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAGO). In intact, untreated animals hypercapnia increased CBF and CMRO2 by approximately 300 and 35%, respectively. Naloxone reduced the hypercapnic increase of CBF, and transformed the hypercapnic increase of CMRO2 into a decrease. The mid-points of the dose-response curves for (1)-naloxone and (d)-naloxone were 10 micrograms/kg and 100 micrograms/kg, respectively. Adrenal demedullation and treatment with (1)-naloxone (0.2 mg/kg) decreased the hypercapnic CBF and CMRO2 by approximately 50%. DAGO treatment of adrenal demedullated animals restored the hypercapnic CBF and CMRO2 to values similar to those found in intact animals. These observations suggest that opioid peptides (most likely adrenal medulla-derived enkephalins) play a significant role in the regulation of CMRO2 and CBF during moderate hypercapnia.
Dora
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Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
Hines
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Kunos
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McLaughlin
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AC
D000313:Adrenal Medulla / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects*; D013237:Stereoisomerism
D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002245:Carbon Dioxide; D009270:Naloxone