Effect of monoamine oxidase inhibition on the regional cerebral blood flow response to circulating noradrenaline.
The effect of an acute i.v. infusion of noradrenaline (NA) on regional cerebral blood flow (rCBF) was investigated in the awake rat using [14C]iodoantipyrine as diffusible tracer. The contribution of vascular monoamine oxidase (MAO) to the efficiency of the enzymatic blood-brain barrier (BBB) to catecholamines was assessed by measuring the multiregional cerebrovascular response to circulating NA given alone or after i.v. administration of the monoamine oxidase inhibitor, clorgyline. Since i.v. infusion of NA elevates blood pressure, the influence of NA on the cerebrovascular bed was first studied by determining the relationship between rCBF and the mean arterial pressure (MAP). When the MAP was only slightly increased (to approximately 130 mm Hg), a trend to flow decrease under NA infusion was observed. Secondly, we compared the effects of NA on rCBF in animals treated or not treated with clorgyline. This was performed under moderate hypertension (within the 'autoregulated' range of MAP) to avoid any risk of mechanical damage to the BBB. Clorgyline administration alone did not significantly modify rCBF, but the subsequent i.v. infusion of NA induced an increase in rCBF (weighted mean 14%) in all structures investigated. The differences being statistically significant (P less than 0.05) in 5 out of 13 structures by up to 20%. Compared to studies involving disruption of the morphological BBB in which plasma NA elicits a widespread important increase in blood flow, the weak cerebrovascular effects we observed provide indirect evidence for the efficiency of the BBB to catecholamines in the conscious rat within the autoregulated range of arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Lasbennes
F
F
Laboratoire de Physiologie et Physiopathologie Cérébrovasculaire, I.N.S.E.R.M., U. 182, C.N.R.S., U.A. 641, Université Paris VII, France.
Lacombe
P
P
Seylaz
J
J
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003010:Clorgyline / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism / Q000502:physiology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; D008995:Monoamine Oxidase; D003010:Clorgyline; D000983:Antipyrine; C008135:iodoantipyrine; D009638:Norepinephrine