Key result
Endothelin-1 dilates cerebral vessels at low doses but drives ischemic vasoconstriction at high doses.
Why the study?
The effects of endothelin-1 on local cortical microvascular perfusion and resistance in the cerebral vasculature were not fully characterized.
Endothelin-1 acts as a potent vasodilator at low doses but causes ischemic vasoconstriction at high doses in the cerebral vasculature of rats, implicating it in cerebral vasospasm.
Answers are grounded in this paper and cite their sources.
Endothelin-1 augments cortical perfusion at low doses in rats; leaves open relevance to human stroke microcirculation.
We used laser-Doppler flowmetry to study the effects of endothelin-1 on local cortical microvascular perfusion and resistance in 29 pentobarbital-anesthetized rats. Intravenous administration of 10-300 pmol endothelin-1 reduced arterial blood pressure and microvascular resistance and increased microvascular perfusion. However, intracarotid administration of low doses of endothelin-1 increased microvascular perfusion and reduced microvascular resistance and arterial blood pressure, whereas high doses (greater than or equal to 300 pmol) reduced microvascular perfusion and increased microvascular resistance and arterial blood pressure. Only the high dose/low flow response was associated with attenuation of the electrocorticogram. The low dose/high flow and high dose/low flow responses to endothelin-1 were not altered by blockade of muscarinic and adrenergic receptors. In addition, systemic metabolic changes (arterial pH, PaCO2, PaO2, and plasma glucose concentration) did not account for the cerebrovascular effects of endothelin-1. Platelet hyperaggregability also did not appear to be a causative factor in the high dose/low flow response to endothelin-1. In fact, ex vivo rat platelet aggregation was inhibited by intracarotid administration of 300 pmol endothelin-1. In conclusion, the cerebral vasculature exhibits extreme sensitivity to the vasodilator properties of endothelin-1 at low doses. The ischemic vasoconstrictor effects observed at high doses implicate endothelin-1 as an important mediator of cerebral vasospasm and/or postischemic hypoperfusion.
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Willette et al. (1990) studied this question. endothelin-1 was evaluated on local cortical microvascular perfusion and resistance. Endothelin-1 acted as a cerebral vasodilator at low doses but caused ischemic vasoconstriction at high doses (≥300 pmol), implicating it in cerebral vasospasm.
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