Chronic endothelin-1 blockade preserves myocardial contractility in dilated cardiomyopathy.
Endothelin-1 (ET-1) is known to have positive inotropic effects in isolated cardiac muscle strips. ET-1 levels are elevated in congestive heart failure (CHF). We investigated the effects of ET-1 on contractility and cardiac relaxation (lusitropy) of the intact healthy murine heart and myocarditic/cardiomyopathic heart by chronic oral treatment with a mixed ETA/ETB blocker SB217242. Chronic ET-1 blockade of normal hearts resulted in depression of contractility and lusitropy of the normal heart but preservation and enhancement of contractility and lusitropy in myocarditic animals, in which ET-1 cardiac content is elevated. This suggests that ET-1 is important in the basal contractility and relaxation of the normal heart but that its chronic elevation in CHF causes impairment of cardiac systolic and diastolic performance.
Pandey
A S
AS
Center for Cardiovascular Research, Toronto Hospital, Ontario, Canada.
Stewart
D J
DJ
Cernacek
P
P
Dawood
F
F
Wen
W H
WH
Liu
P
P
D000818:Animals; D002264:Carboxylic Acids / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009200:Myocardial Contraction / Q000187:drug effects*; D009205:Myocarditis / Q000188:drug therapy / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D044022:Receptor, Endothelin A
D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007189:Indans; D044022:Receptor, Endothelin A; C098288:enrasentan