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 endoge nous morphine-like substances (endorphins), and the possible interaction be tween these two Systems in the modulation of regional cerebral and spinal C O2 responsiveness was investigated in anesthetized, ventilated, normotensiv e, normoxic cats. Regional cerebral blood flow was measured with radiolabel ed microspheres in hypocapnic, normocapnic, and hypercapnic conditions in n ine individual cerebral and spinal cord regions. General opiate receptor bl ockade 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 c aused no changes in regional CO2 responsiveness. Combined administration of these two blocking agents in the very same doses, however, resulted in a s trong potentiation, with a statistically significant reduction of the CO2 r esponsiveness observed. Separation of the blood flow response to hypercapni a and hypocapnia indicates that this reduction occurs only during hypercapn ia. 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 r ole 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 responsivenes s. The current findings suggest a previously unknown interaction between th e endothelium-derived relaxing factor/nitric oxide (EDRF/NO) system and the endogenous opiate system in the cerebrovascular bed during hypercapnic sti mulation, with the phenomenon not mediated by mu or delta opiate receptors.