Central and regional hemodynamic effects during infusion of big
endothelin-1 in healthy humans.
Ahlborg, Gunvor, Astrid Ottosson-Seeberger, Anette Hems[acute]en, and
Jan M Lundberg.
Huddinge University Hospital, S-141 86 Huddinge, Sweden: Department
of Clinical Physiology: G Ahlborg; Department of Renal Medicine: A
Ottosson-Seeberger; Department of Physiology and Pharmacology,
Karolinska Institute, Stockholm, Sweden: A Hems[acute]en, J M
Lundberg.
APStracts 3:0032A, 1996.
Big endothelin-1 (big ET-1) was given intravenously to six healthy
males to study uptakes and vascular effects. Blood samples were taken
from systemic (A) and pulmonary arterial, internal jugular (JV) and
deep forearm (DV) venous catheters. Arterial big ET-1-like
immunoreactivities (LI) increased from 5.43+/-0.60 to 756+/-27
pmol.l-1, and ET-1-LI from 4.67+/-0.08 to 6.67+/-0.52 pmol.l-1
(p<0.001). Skeletal muscle fractional extraction of big ET-1-LI
was (15+/-4%). ET-1-LI release did not increase in the studied
vascular beds. Heart rate (HR) fell by 17% (p<0.001), cardiac
output (CO) by 26% (p<0.001), and stroke volume (SV) by 11%
(p<0.05). Mean arterial blood pressure (MAP) (18%), systemic
(SVR) (65%) and pulmonary (PVR) (57%) vascular resistance increased
(p<0.01-0.001). Pulmonary blood pressures, forearm blood flow,
arterial pH, arterial pCO2, and (A-JV)O2, remained unchanged. No
specific big ET-1 receptors were found in human pulmonary membranes.
IC50 for the receptor antagonist bosentan was 181 nM. Summary:
Circulating big ET-1 elicits greater increases in MAP and SVR and
decreases in HR and CO compared to equimolar ET-1 infusion (26).
Received 24 July 1995; accepted in final form 3 January 1996.
APS Manuscript Number A802-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96