Received August 10, 2004
Revised September 15, 2004
Accepted after revision October 4, 2004
Neuronal activity-related coupling in cortical arterioles - involvement of astrocyte-derived factors
Thelma A Lovick 1*,
Brian J Key 1,
Laurence A Brown 2
1 University of Birmingham
2 University of Oxford
* To whom correspondence should be addressed. E-mail: t.a.lovick{at}bham.ac.uk.
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Abstract |
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Neuronal activity-evoked dilatation was investigated in cortical arterioles in brain slices from mature rats and maintained in vitro at 31-33oC. In the presence of the thromboxane A2 agonist U46619 (75nM) to pre-constrict vessels, internal diameter decreased by14.2% and rhythmic contractile activity (vasomotion) developed. Addition of the epoxygenase inhibitor miconazole (20mM) produced a further decrease in diameter and increase in the frequency of vasomotion suggesting that tonic release of epoxygenase products maintains a level of cerebrovascular dilator tone.
Addition of 1mM AMPA for 5min evoked a 15.4±3.7% increase in diameter and the frequency of vasomotion decreased by -6.7±1.4 contractions min-1. The response persisted in the presence of 1mM TTX indicating that it was independent of neuronal activity and thus likely to have been evoked by activation of AMPA receptors on astrocytes rather than neurones. The response to the brief (5min) application of AMPA remained unchanged in the presence of miconazole (20mM). Prolonged (30 min) application of AMPA produced a +12.1±1.5% increase in internal diameter and reduction in vasomotion (-8.4±1.7 min-1) that were sustained throughout the stimulation period. However, when AMPA was applied in the presence of miconazole (20mM) it evoked only a transient increase in diameter (+9.8±3.1%) and decrease in vasomotion (-6.6±1.5 min-1) that lasted for less than 10-min despite continued application of AMPA.
The results suggest that products of epoxygenase activity, probably epoxyeicosatrienoic acids (EETs) are involved in activity-related dilatation in cortical arterioles. Whilst epoxygenase activity is not required to initiate dilatation, it appears to be involved in sustaining the response. Thus EETs released from membrane stores could contribute to the initial stages but once these have been depleted, de novo synthesis of EETs is required to maintain the effect.
Key Words:
Brain, Glia, Vasodilatation
