Opioids in cerebrospinal fluid in hypotensive newborn pigs.
This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. Closed cranial windows were used to determine pial arteriolar diameter. Periarachnoid cortical and cisterna magna CSF was collected from piglets during normotension and hypotension (systemic arterial pressure decreased from 63 +/- 1 to 33 +/- 1 mm Hg). Opioid profiles were assessed qualitatively by radioreceptor assay, and individual opioids were measured quantitatively by radioimmunoassay. Periarachnoid cortical and cisterna magna CSF methionine enkephalin-, leucine enkephalin-, dynorphin-, and beta-endorphin-like receptor active values all were increased by hypotension. When quantified by radioimmunoassay, periarachnoid cortical CSF values for methionine enkephalin-like immunoreactivity were 1,167 +/- 58 and 2,975 +/- 139 pg/ml for normotension and hypotension, respectively. Periarachnoid cortical CSF radioimmunoassay values for dynorphin-like immunoreactivity were 15 +/- 2 and 28 +/- 2 pg/ml for normotension and hypotension, respectively. When applied topically to the cortical surface, synthetic methionine enkephalin increased pial arteriolar diameter (134 +/- 4, 158 +/- 4, and 163 +/- 4 microns for control, 574 pg/ml [10(-10) M], and 5,740 pg/ml [10(-9) M], respectively). Similarly, topical synthetic leucine enkephalin and dynorphin elicited pial arteriolar dilation. However, beta-endorphin produced arteriolar constriction. Hypotension attenuated methionine and leucine enkephalin-induced dilation and reversed dynorphin-induced dilation to concentration-dependent constriction. beta-Endorphin-induced constriction was not changed by hypotension. Therefore, opioids could contribute to the control of the cerebral circulation during hypotension.
Armstead
W M
WM
Department of Physiology, University of Tennessee, Memphis 38163.
Mirro
R
R
Busija
D W
DW
Desiderio
D M
DM
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D004399:Dynorphins / Q000134:cerebrospinal fluid / Q000494:pharmacology; D004723:Endorphins / Q000134:cerebrospinal fluid*; D004743:Enkephalin, Leucine / Q000134:cerebrospinal fluid / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000134:cerebrospinal fluid / Q000494:pharmacology; D006470:Hemorrhage / Q000134:cerebrospinal fluid; D007022:Hypotension / Q000134:cerebrospinal fluid*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011863:Radioimmunoassay; D011869:Radioligand Assay; D012016:Reference Values; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D001615:beta-Endorphin / Q000134:cerebrospinal fluid / Q000494:pharmacology
D004723:Endorphins; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D004399:Dynorphins