Modification of systemic and regional circulatory effects of intracerebroventricular administration of endothelin-1 by propranolol in anesthetized rats.

1. Cardiovascular effects of centrally administered endothelin-1 (ET-1) were studied in control and propranolol-treated anesthetized rats using a radioactive microsphere technique. 2. In the control group, blood pressure, cardiac output, and stroke volume were decreased, and heart rate was not altered after the administration of ET-1.ET-1 produced a reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system, and skin. 3. Propranolol significantly attenuated the decrease in blood pressure, cardiac output and stroke volume induced by centrally administered ET-1. The reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system and skin induced by centrally administered ET-1 was blocked by propranolol. 4. It is concluded that centrally administered ET produces significant cardiovascular effects which are mediated through the sympathetic nervous system and could be antagonized by propranolol. These findings can also be helpful in explaining some of the beneficial effects of propranolol in various cardiovascular disorders involving central ET mechanisms.