CARDIOVASCULAR EFFECTS OF CENTRALLY ADMINISTERED ENDOTHELIN-1 IN RATS

The effect of centrally administered endothelin-1 (ET-1) or IRL 1620 ( 5, 15, and 45 ng) on systemic hemodynamics was studied in anesthetized rats using a radioactive microsphere technique. Administration of sal ine (5 mu l, i.c.v.) did not product any significant cardiovascular ef fects. The lower doses of ET-1 (5 and 15 ng) did not produce any signi ficant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR). Howev er, the highest dose (45 ng) produced a transient rise followed by a s ustained fall in BP. The CO and SV decreased significantly, whereas HR and TPR were not affected. Pretreat ment with BQ-123 (10 mu g, i.c.v. ) 15 min before administration of ET-1, completely antagonized the sys temic hemodynamic effects of ET-1. Centrally administered IRL 1620, a specific ET(B) receptor agonist, did not produce any effect on BP, HR, CO, SV, and TPR in rats. It is concluded that ET(A) but not ET(B) rec eptors are involved in the central cardiovascular actions of ET.