Effect of monoamine oxidase inhibition on the regional cerebral blood flow response to circulating noradrenaline |
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Authors: | Francois Lasbennes Pierre Lacombe Jacques Seylaz |
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Institution: | Franc¸ois Lasbennes, Pierre Lacombe,Jacques Seylaz |
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Abstract: | 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 or 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 < 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. Conversely, the NA-induced vasodilation obtained after inhibition of vascular MAO shows that the enzymatic BBB participates in the overall restriction of the permeability to NA, with a fairly homogeneous regional distribution. |
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Keywords: | Local cerebral blood flow Blood-brain barrier Autoregulation Monoamine oxidase inhibitor |
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