Interactions between the endothelium-derived relaxing factor/nitric oxide system and the endogenous opiate system in the modulation of cerebral and spinal vascular CO2 responsiveness.
The role of the L-arginine-nitric oxide (NO) system, the role of the endogenous morphine-like substances (endorphins), and the possible interaction between these two systems in the modulation of regional cerebral and spinal CO2 responsiveness was investigated in anesthetized, ventilated, normotensive, normoxic cats. Regional cerebral blood flow was measured with radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions in nine individual cerebral and spinal cord regions. General opiate receptor blockade by 1 mg/kg naloxone intravenously alone or NO synthase blockade by 3 mg/kg N(omega)-nitro-L-arginine-methyl ester (L-NAME) intravenously alone caused no changes in regional CO2 responsiveness. Combined administration of these two blocking agents in the very same doses, however, resulted in a strong potentiation, with a statistically significant reduction of the CO2 responsiveness observed. Separation of the blood flow response to hypercapnia and hypocapnia indicates that this reduction occurs only during hypercapnia. Specific mu and delta opiate receptors were blocked by 0.5 mg kg(-1) IV beta-funaltrexamine and 0.4 mg kg(-1) IV naltrindole, respectively. The role of specific mu and delta opiate receptors in the NO-opiate interaction was found to be negligible because neither mu nor delta receptor blockade along with simultaneous NO blockade were able to decrease CO2 responsiveness. The current findings suggest a previously unknown interaction between the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) system and the endogenous opiate system in the cerebrovascular bed during hypercapnic stimulation, with the phenomenon not mediated by mu or delta opiate receptors.
Komjáti
K
K
Cerebrovascular Research Center, University of Pennsylvania, Philadelphia, PA, USA.
Greenberg
J H
JH
Reivich
M
M
Sándor
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D002415:Cats; D002560:Cerebrovascular Circulation; D008297:Male; D009294:Narcotics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011957:Receptors, Opioid / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
D009294:Narcotics; D011957:Receptors, Opioid; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III