Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1
Open Access
- 1 July 2004
- journal article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 63 (1) , 41-50
- https://doi.org/10.1016/j.cardiores.2004.03.016
Abstract
Objective: The pulmonary circulation may contribute to elevated plasma levels of endothelin-1 (ET-1) in congestive heart failure (CHF). The aims of the present study were to determine the mechanisms of increased secretion of ET-1 from the pulmonary circulation in CHF. Methods: Juvenile pigs were subjected to sham operation (n=9) or rapid cardiac pacing-induced CHF (215–240 bpm, n=15). Results: Three weeks of rapid pacing led to significant left ventricular dilatation, increased cardiac filling pressures, and reduced contractility (CHF pigs). Arterial plasma ET-1 levels in the CHF pigs were increased 4-fold compared to sham pigs (P−1·mg protein−1) was selectively increased in lower lobe segments of CHF pigs (2.0±0.3) compared to lower lobe segments of controls (1.1±0.1, PPR=0.75, PConclusions: In rapid pacing-induced CHF, a complex cardiopulmonary interaction revealed by pulmonary congestion causes increased pulmonary production and secretion of ET-1 due to enhanced pulmonary ECE-1 activities. Pulmonary secretion of ET-1 during evolving CHF is an important contributor to elevated plasma ET-1 levels in the systemic circulation.Keywords
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