Impact of treatment with melatonin on cerebral circulation in old rats.

Melatonin deprival in young rats induces alterations in cerebral arteriolar wall similar to those observed during aging: atrophy and a decrease in distensibility. In this study, we examined the effects of melatonin treatment on cerebral arteriolar structure and distensibility and on the lower limit of cerebral blood flow autoregulation (LLCBF) in old rats. We measured cerebral blood flow (arbitrary unit, laser Doppler, open skull preparation) prior to and during stepwise hypotension (SH) in adult (12/13 months) and old (24/25 months) IcoWI and WAG/Rij male rats. Old rats were untreated or treated for 3 months with melatonin (0.39 (IcoWi) and 0.44 (Wag/Rij) mg kg-1 day-1, drinking water). Stress-strain relationships were determined using cross-sectional area (CSA, microm2, histometry) and values of arteriolar internal diameter (microm) obtained during a second SH following arteriolar deactivation (EDTA, 67 mmol l(-1)). Aging induced (a) atrophy of the arteriolar wall in IcoWI (616+/-20 vs 500+/-27 microm2, P<0.05) but not in WAG/Rij rats (328+/-25 vs 341+/-20 microm2), (b) a decrease in arteriolar wall distensibility and (c) an increase in the LLCBF in both strains (67+/-10 mmHg in 12-month-old vs 95+/-6 mmHg in 24-month-old IcoWi, P<0.05 and 53+/-2 mmHg in 13-month-old vs 67+/-6 mmHg in 25-month-old WAG/Rij). Melatonin treatment induced in IcoWI and WAG/Rij rats (a) hypertrophy of the arteriolar wall (643+/-34 and 435+/-25 microm2, respectively), (b) an increase in arteriolar wall distensibility and (c) a decrease in the LLCBF (64+/-6 and 45+/-4 mmHg, respectively). Melatonin treatment of old rats induced hypertrophy of the arteriolar wall, prevented the age-linked decrease in cerebral arteriolar distensibility and decreased the LLCBF. British Journal of Pharmacology (2004) 141, 399-406. doi:10.1038/sj.bjp.0705629