Hemodynamic effects of endothelin in conscious rats.
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 micrograms/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.
Hinojosa-Laborde
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Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Osborn
J W
JW
Cowley
A W
AW
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D002714:Chlorisondamine / Q000494:pharmacology; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012018:Reflex; D012602:Scopolamine Derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D016232:Endothelins; D010276:Parasympatholytics; D010455:Peptides; D012602:Scopolamine Derivatives; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D002216:Captopril; D002714:Chlorisondamine; D019832:N-Methylscopolamine