Opiate receptor-mediated mechanisms in the regulation of cerebral blood flow.
Endogenous opioid peptides are present in cerebral perivascular nerves and in the CSF, and their concentrations are changing in response to stimuli that activate regulatory mechanisms of the cerebral circulation (e.g., alterations of the perfusion pressure or changes of the arterial O2 tension). Opiate receptors are expressed in the cells of the CNS and the cerebrovascular bed, and their activation modulates the function of other vasoregulatory mechanisms (i.e., the autonomic nervous system, nitric oxide, prostanoids, vasopressin) that are involved in the control of the cerebrovascular tone. The direct vasomotor effects of opioid peptides and opiates on the cerebral arteries under in vitro or in situ conditions appear to be weak or absent in several species. However, Met- and Leu-enkephalin induce pial arterial vasodilation in the newborn pig. In this species, beta-endorphin acts as a constrictor, whereas dynorphin may induce either dilation or constriction depending on the experimental conditions. The influence of exogenously applied natural and synthetic opioids on the cerebral blood flow (CBF) is determined mainly by their metabolic, neuronal, and respiratory effects. Hypothalamic and pituitary circulations are especially sensitive to opioids. Under resting conditions, endogenous opioid peptides do not participate in the regulation of the cerebrovascular tone and CBF. On the other hand, mu and delta opiate receptor stimulation by endogenous opioid peptides, interacting with other vasoactive factors, obviously contributes to the hypoxia- and hypercapnia-induced cerebral vasodilation. Furthermore, endogenous opioid mechanisms are involved in the autoregulation of the hypothalamic blood flow. Thus, the endogenous opioid system may well represent a latent regulatory mechanism, which is of limited importance under basal conditions, but becomes more important under conditions of stress. Synthetic exogenous opioids do not appear to influence the hypoxic or hypercapnic CBF responses or the cerebral autoregulatory process.
Benyó
Z
Z
Department of Physiology, Ludwig Maximilians University, Munich, Germany.
Wahl
M
M
D001923:Brain Chemistry / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D011957:Receptors, Opioid / Q000502:physiology*
D011957:Receptors, Opioid