EFFECTS OF INTRACISTERNAL ENDOTHELIN-1 INJECTION ON BLOOD-FLOW TO THE LOWER BRAIN-STEM

The central effects of endothelin-1 (Et-1, 10-30 pmol in 2.5-mu-l injected intracisternally) have been investigated in the conscious rat. With 10 and 20 pmol Et-1, no significant change in blood pressure was observed. With 30 pmol Et-1, mean arterial blood pressure rose by 40 +/- 10 mm Hg with an accompanying modest, short-lived bradycardia at 2 min post-injection. Cerebral blood flow ([C-14]iodoantipyrine autoradiography), measured simultaneously with the hypertensive response, was markedly reduced throughout the caudal medulla and cerebellum (by up to 85%), while significant hyperaemia was evident in a number of forebrain structures (e.g. an increase of 78% in sensorimotor cortex). These observations have relevance to two distinct scientific areas. Concerning the significant effect of Et-1 in central cardiovascular control, these results caution against drawing conclusions from ventricular application with knowledge only of cardiovascular parameters. These results also illustrate the profound effects of Et-1 which is uniquely capable of overriding cerebral autoregulatory mechanisms.