Cardiovascular effects of centrally administered endothelin-1 and its relationship to changes in cerebral blood flow.
Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng. i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (-40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (-46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on Blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 micrograms, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET receptors.
Gulati
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A
Department of Pharmaceutics & Pharmacodynamics, The University of Illinois at Chicago, Chicago IL 60612, USA.
Kumar
A
A
Shahani
B T
BT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002302:Cardiac Output / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins