The role of endothelin-1 in pressure autoregulation of cerebral blood flow in rats.

Abstract

To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats. We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure-intracranial pressure) with norepinephrine (0.08 microgram.kg-1.min-1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ETA/B receptor antagonist, bosentan, i.v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique. During the control test, norepinephrine infusion increased CPP by 21 +/- 2 (23 +/- 2%) mmHg (mean +/- SEM; p < 0.001) and CBF by 3.6 +/- 3.1 (6 +/- 8%) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 +/- 1 (20 +/- 2%) mmHg (p < 0.001) and CBF by 15.8 +/- 4.1 (46 +/- 13%) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaCO2 levels were stable during the tests (40.2 +/- 1.4 mmHg). The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.