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Regional effects and clearance of endothelin‐1 across pulmonary and splanchnic circulation
Author(s) -
WAGNER O. F.,
VIERHAPPER H.,
GASIC S.,
NOWOTNY P.,
WALDHÄUSL W.
Publication year - 1992
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1992.tb01463.x
Subject(s) - splanchnic , vascular resistance , splanchnic circulation , medicine , pulmonary artery , cardiac output , hemodynamics , cardiology , endothelin 1 , endocrinology , receptor
. To determine the impact of i.v. endothelin‐1 on systemic, pulmonary and splanchnic circulation, as well as the peptide's regional clearance, hepatic venous and right heart catheterization was performed in healthy volunteers. During the peptide's continuous i.v. administration (0.4 pmol x kg ‐1 x min ‐1 , 60 min) its plasma concentration rose from 21±0.5 to 9.5 ± 5.3 pmol/1 (pulmonary artery), from 2.1±0.9 to 5.0±1.6 pmol/1 (femoral artery), and from 1.5 ± 0.6 to 2.9±1.2 pmol/1 (hepatic vein). This was accompanied by an increase in mean systolic arterial pressure from 127±14 to 131 ± 12mmHg( P <0.05). Concomitantly, cardiac output and heart rate decreased from 7.0 ±1.1 to 5.8 ±1.01/min and from 63 ± 6 to 56 ± 5 beats/min, respectively, while total vascular resistance increased from 964 ± 273 to 1204 ±338 dyn x cm x s ‐5 ( P <0.01). No major changes in pulmonary circulation were observed, while splanchnic vascular resistance increased from 4472±1056 to 5361 ± 1420 dyn x cm x s ‐5 ( P <0.01) and estimated hepatic blood flow decreased from 1403 ± 218 to 1218 ± 219 ml min ‐1 ( P <0.01). During endothelin‐1 infusion the pulmonary vascular bed accounted for approximately 53% of the peptide's overall disposal. Since the splanchnic area receives blood previously cleared during passage across the pulmonary vascular bed and the splanchnic plasma flow represented only 25 to 30% of the pulmonary plasma flow, the absolute amount of endothelin‐1 disposed in the splanchnic region represented only about 3%. However, the regional fractional extraction rates were comparable (mean splanchnic fractional extraction: 35.5 ± 2.1 %; mean pulmonary fractional extraction: 49.2 ± 14.9%), and thereby indicate a potentially similar efficacy of the pulmonary and splanchnic vascular bed to extract endothelin‐1. In conclusion we showed pulmonary clearance to be a main cause of the short half‐life of endothelin‐1 in man. Furthermore, the hemodynamic changes induced by the slight increases in regional concentrations of endothelin‐1 provide evidence for a role of endothelin‐1 in the regulation of circulation under (patho‐) physiological conditions.