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

Abstract

Objective: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats. Design: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure-intracranial pressure) with norepinephrine (0.8 μg.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 ET(A/B) receptor antagonist, bosentan, i.v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique. Results: 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). Conclusions: 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.