Hemodynamic effects of endothelin in conscious rats

C. Hinojosa-Laborde, J. W. Osborn, A. W. Cowley

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The hemodynamic responses to endothelin, a recently isolated vasoconstrictor peptide, were determined in conscious rats with and without the three major known neurohumoral control systems. Rats (n = 6) were instrumented with arterial and venous catheters and an electromagnetic flow probe around the ascending aorta. Neurohumoral blockade was achieved with 10 mg/kg chlorisondamine, 0.5 mg/kg methscopolamine, 1 mg/kg captopril, and 10 μg/kg d(CH2)Tyr5(Me)AVP. Resting mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) in areflexic rats were restored to normal levels with a constant norepinephrine infusion. Endothelin was infused intravenously for 25 min in doses ranging from 0.01 to 1,000 ng·kg-1·min-1. Rats with intact reflexes did not respond significantly until a dose of 100 ng·kg-1·min-1 that increased MAP 20%, decreased CO 22% and increased TPR 58%. At a dose of 1,000 ng·kg-1·min-1 of endothelin (infused for 10 min), MAP increased 35%, CO decreased 66%, and TPR increased 303%. In areflexic rats, 1 ng·kg-1·min-1 of endothelin caused significant increases in MAP (14%), small decreases in CO (-5%), and a 20% increase in TPR. At a dose of 10 ng·kg-1·min-1, MAP increased 17%, CO decreased 3%, and TPR increased 21%; at 100 ng·kg-1·min-1, MAP increased 40%, CO decreased 13%, and TPR increased 67%; at 1,000 ng·kg-1·min-1, MAP increased 48%, CO decreased 61%, and TPR increased 319%. The pressor effects of endothelin were therefore significantly buffered by neurohumoral systems; however, the decreases in CO caused by high doses of endothelin were independent of neurohumoral control.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number6
StatePublished - Jan 1 1989


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