Basal cerebral blood flow is dependent on the nitric oxide pathway in elderly but not in young healthy men.
OBJECTIVE
Brain perfusion is tightly regulated over a wide range of blood pressures by local regulation of cerebral blood flow (CBF). Ageing is associated with impaired CBF and impaired nitric oxide mediated vasodilator responses. The role of nitric oxide in the regulation of basal CBF in young and older subjects was investigated, using the nitric oxide synthase inhibitor L-NMMA as pharmacological tool.


METHODS
We used a gradient echo phase-contrast magnetic resonance imaging technique to investigate the role of nitric oxide in the regulation of cerebral blood flow in young (25+/-7.1 years; n=8) and old (78+/-6.6 years; n=7) volunteers. The study was performed in a double-blinded fashion and consisted of two study days. On one day the effects of the intravenously infused L-NMMA on CBF and blood pressure was measured and on the other day the effects of a matching placebo.


RESULTS
Basal CBF was significantly lower in old compared to young subjects (590+/-20 vs 704+/-20 ml/min), while the cerebral vascular resistance (CVR) levels were significantly higher (0.15+/-0.01 (arbitrary units) vs 0.12+/-0.01, respectively). Infusion of L-NMMA significantly increased mean arterial pressure in both groups (2.8+/-1.2 mmHg; p=0.02 in the young and in the old subjects 5.6+/-1.1 mmHg; p<0.001). Infusion of L-NMMA significantly decreased CBF (49+/-12 ml/min; p<0.001) and increased CVR (0.02+/-0.004; p<0.001) in the old subjects but did not significantly influence cerebral circulation in the young subjects.


CONCLUSIONS
We conclude that compared to young subjects, in old people CBF is impaired, and dependent on the intactness of the nitric oxide pathway.
Department of General Internal Medicine, Section of Gerontology and Geriatrics, C1-R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. a.m.kamper@lumc.nl
Adriaan M
AM
Kamper
Aart
A
Spilt
Anton J M
AJ
de Craen
Mark A
MA
van Buchem
Rudi G J
RG
Westendorp
Gerard J
GJ
Blauw
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D016022:Case-Control Studies; D004311:Double-Blind Method; D006706:Homeostasis; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine
D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase