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 cerebr al arteriolar tone and the melatonin-induced shift in cerebral blood flow ( CBF) autoregulation to a lower pressure level. Using the cranial window tec hnique, we showed that intravenous infusion of melatonin constricted pial a rterioles (-5.1 +/- 1.3 and -5.4 +/- 0.7 mum at 60 and 600 ng/kg/h, respect ively). Perivascular application of luzindole alone had no significant effe ct but abolished vasoconstriction induced by melatonin (-0.5 +/- 0.7 and 3.0 +/- 1.2 mum at 60 and 600 ng/kg/h respectively). Using a combination of the hydrogen clearance and cranial window techniques, we showed that intra venous infusion of melatonin had no effect on baseline CBF but shifted the lower limit (LL) of CBF autoregulation (stepwise hypotension) to a lower pr essure (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 autoregulat ion, the security margin increased (28 +/- 5 in controls vs. 38 +/- 3 and 5 5 +/- 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 arteri olar dilatory response to hypotension but did not increase absolute diamete r at any given pressure level. Our results show that melatonin shifts the L L of CBF autoregulation to a lower systemic pressure level. This effect doe s not appear to be explained by the effect of melatonin on cerebral arterio lar diameter.