Differential uptake of endothelin-1 by the coronary and pulmonary circulations.
Substantial removal of the vasoconstrictor peptide endothelin-1 (ET-1) by the pulmonary circulation has been reported to occur in perfused guinea pig and rat lungs. We examined the uptake of ET-1 by coronary and pulmonary circulations of the rabbit by measuring single-pass extraction of ET-1 in the isolated heart and lung. In separate experiments, each organ was perfused at 30 ml/min with Krebs-albumin (3%) solution. A bolus of 125I-ET-1 and [14C]dextran in 0.3 ml Krebs-albumin solution was injected, and extraction of endothelin (EET), relative to that of an intravascular reference indicator, [14C]dextran, was determined by multiple indicator-dilution technique. EET was 5 +/- 2% (SE) in the heart and 49 +/- 4% in the lung. Increasing flow rate in the lung preparation to approximate the mean transit time in the heart preparation did not significantly alter EET. Despite insignificant uptake of ET-1, the coronary circulation extracted an angiotensin-converting enzyme inhibitor (351A) and metabolized a synthetic angiotensin-converting enzyme substrate (benzoyl-phenyl-alanyl-proline), both properties of the normal pulmonary circulation. We therefore conclude that there is no significant ET-1 uptake in the coronary vascular bed.
Rimar
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Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Gillis
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003911:Dextrans; D016232:Endothelins / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008168:Lung / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000502:physiology; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D003911:Dextrans; D016232:Endothelins; D007457:Iodine Radioisotopes