Melatonin increases pial artery tone and decreases the lower limit of cerebral blood flow autoregulation.
We studied a possible link between the melatonin-induced increase in cerebral arteriolar tone and the melatonin-induced shift in cerebral blood flow (CBF) autoregulation to a lower pressure level. Using the cranial window technique, we showed that intravenous infusion of melatonin constricted pial arterioles (-5.1 +/- 1.3 and -5.4 +/- 0.7 microm at 60 and 600 ng/kg/h, respectively). Perivascular application of luzindole alone had no significant effect but abolished vasoconstriction induced by melatonin (-0.5 +/- 0.7 and + 3.0 +/- 1.2 microm at 60 and 600 ng/kg/h respectively). Using a combination of the hydrogen clearance and cranial window techniques, we showed that intravenous infusion of melatonin had no effect on baseline CBF but shifted the lower limit (LL) of CBF autoregulation (stepwise hypotension) to a lower pressure (90 +/- 2 mmHg in vehicle vs. 71 +/- 3 and 51 +/- 5 mmHg, both P < 0.05, after melatonin at 60 and 600 ng/kg/h, respectively). As melatonin had no effect on systemic blood pressure yet shifted the LL of CBF autoregulation, the security margin increased (28 +/- 5 in controls vs. 38 +/- 3 and 55 +/- 5% after melatonin at 60 and 600 ng/kg/h, respectively, both P < 0.05). The higher i.v. infusion rate of melatonin increased the relative arteriolar dilatory response to hypotension but did not increase absolute diameter at any given pressure level. Our results show that melatonin shifts the LL of CBF autoregulation to a lower systemic pressure level. This effect does not appear to be explained by the effect of melatonin on cerebral arteriolar diameter.
Régrigny
O
O
Laboratoire de Pharmacologie Cardiovasculaire, EA 3116, Faculté de Pharmacie, Université Henri Poincaré-Nancy I, 5 rue Albert Lebrun, 54000 Nancy, France.
Delagrange
P
P
Scalbert
E
E
Atkinson
J
J
Chillon
J M
JM
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010841:Pia Mater / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D044094:Receptors, Melatonin; D014363:Tryptamines / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D016166:Free Radical Scavengers; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D008550:Melatonin