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Hemodynamic effects of endothelin in conscious rats. Am J Physiol 1989 Jun;256(6 Pt 2):H1742-6

Date

06/11/1989

Pubmed ID

2660597

DOI

10.1152/ajpheart.1989.256.6.H1742

Scopus ID

2-s2.0-0024312814 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

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.

Author List

Hinojosa-Laborde C, Osborn JW Jr, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arginine Vasopressin
Blood Pressure
Captopril
Cardiac Output
Chlorisondamine
Endothelins
Endothelium, Vascular
Heart Rate
Hemodynamics
Male
N-Methylscopolamine
Parasympatholytics
Peptides
Rats
Rats, Inbred Strains
Reference Values
Reflex
Scopolamine Derivatives
Vascular Resistance