Regional effects and clearance of endothelin-1 across pulmonary and splanchnic circulation

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 2.1 +/- 0.5 to 9.5 +/- 5.3 pmol/l (pulmonary artery), from 2.1 +/- 0.9 to 5.0 +/- 1.6 pmol/l (femoral artery), and from 1.5 +/- 0.6 to 2.9 +/- 1.2 pmol/l (hepatic vein). This was accompanied by an increase in mean systolic arterial pressure from 127 +/- 14 to 131 +/- 12 mmHg (P less than 0.05). Concomitantly, cardiac output and heart rate decreased from 7.0 +/- 1.1 to 5.8 +/- 1.0 l/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 less than 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 less than 0.01) and estimated hepatic blood flow decreased from 1403 +/- 218 to 1218 +/- 219 ml min-1 (P less than 0.01). During endothelin-1 infusion the pulmonary vascular bed accounted for approximately 53% of the peptide's overall disposal.(ABSTRACT TRUNCATED AT 250 WORDS)