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

Objective:To investigate the role of the endothelin system in pressure auto regulation of cerebral blood flow (CBF) in rats. Design: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure-intracranial pressure) with norepinep hrine(0.08 mu g.kg(-1).min(-1) for 30 min) twice in ten anesthetized normoc apnic rats. The first test was performed without (control test) and the sec ond test after administration of the combined endothelin ETA/B receptor ant agonist, bosentan, i.v. (30 mg/kg; drug test). CBF was measured by the hydr ogen clearance technique. Results: During the control test, norepinephrine infusion increased CPP by 21 +/- 2 (23 +/- 2%) mmHg (mean I 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 lest, norepinephri ne 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 pressu re was not affected by bosentan infusion (p = 0.2), PaCO2 levels were stabl e during the tests (40.2 +/- 1.4 mmHg), Conclusions: The endothelin system is involved in cerebral pressure autoreg ulation in a rodent model in vivo. The role of this system under pathophysi ologic conditions such as subarachnoid hemorrhage, where basal vascular ton e and its regulation may be altered, remains to be defined.