Peripheral venous congestion causes time- and dose-dependent release of endothelin-1 in humans.
Endothelin-1 (ET-1) is a pivotal mediator of vasoconstriction and inflammation in congestive states such as heart failure (HF) and chronic kidney disease (CKD). Whether peripheral venous congestion (VC) increases plasma ET-1 at pressures commonly seen in HF and CKD patients is unknown. We seek to characterize whether peripheral VC promotes time- and dose-dependent increases in plasma ET-1 and whether these changes are sustained after decongestion. We used a randomized, cross-over design in 20 healthy subjects (age 30 ± 7 years). To experimentally model VC, venous pressure was increased to either 15 or 30 mmHg (randomized at first visit) above baseline by inflating a cuff around the subject's dominant arm; the nondominant arm served as a noncongested control. We measured plasma ET-1 at baseline, after 20, 60 and 120 min of VC, and finally at 180 min (60 min after cuff release and decongestion). Plasma ET-1 progressively and significantly increased over 120 min in the congested arm relative to the control arm and to baseline values. This effect was dose-dependent: ET-1 increased by 45% and 100% at VC doses of 15 and 30 mmHg, respectively (P<0.05), and declined after 60 min of decongestion though remaining significantly elevated compared to baseline. In summary, peripheral VC causes time- and dose-dependent increases in plasma ET-1. Of note, the lower dose of 15 mmHg (more clinically relevant to HF and CKD patients) was sufficient to raise ET-1. These findings support the potentially contributory, not merely consequential, role of VC in the pathophysiology of HF and CKD.
Columbia University Medical Center, New York, New York.
Jeffrey
J
Lin
Columbia University Medical Center, New York, New York.
Neelesh
N
Chudasama
Columbia University Medical Center, New York, New York.
Yacki
Y
Hayashi
Columbia University Medical Center, New York, New York.
Christopher
C
Hawk
Columbia University Medical Center, New York, New York.
Sahadeo D
SD
Ramnauth
Columbia University Medical Center, New York, New York.
Ka Yuk
KY
Wong
Columbia University Medical Center, New York, New York.
Ante
A
Harxhi
Columbia University Medical Center, New York, New York.
Duygu
D
Onat
Columbia University Medical Center, New York, New York.
Michiyori
M
Wakabayashi
Columbia University Medical Center, New York, New York.
Nir
N
Uriel
Columbia University Medical Center, New York, New York.
Ulrich P
UP
Jorde
Tulane University School of Medicine, New Orleans, Louisiana.
Thierry H
TH
LeJemtel
Medicine, Henry Ford Hospital, Detroit, Michigan.
Hani N
HN
Sabbah
Columbia University Medical Center, New York, New York.
Ryan T
RT
Demmer
Columbia University Medical Center, New York, New York pcc2001@columbia.edu.
Paolo C
PC
Colombo
D000328:Adult; D018592:Cross-Over Studies; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D013997:Time Factors; D014661:Vasoconstriction / Q000502:physiology*; D014690:Venous Pressure / Q000502:physiology*; D055815:Young Adult
D019332:Endothelin-1
Congestive heart failure; endothelin; inflammation