ENDOTHELIN-1 MYOCARDIAL CLEARANCE, PRODUCTION, AND EFFECT ON CAPILLARY-PERMEABILITY IN-VIVO

Myocardial metabolism of endothelin-1 (ET-1) and its effect on coronar y microcirculatory exhanges were obtained in anesthetized dogs by comb ining the indicator-dilution technique with immunoreactive ET-1 measur ements. The myocardium extracted 17.7 +/- 4.6% of tracer ET-1 (n = 12) . Simultaneously measured ET-1 levels in the aorta (0.97 +/- 0.46 pg/m l) and coronary sinus (0.96 +/- 0.53 pg/ml) were not different, suppor ting a production of ET-1 by the heart that balances the amount extrac ted. Intracoronary infusion of ET-1 (5 ng . kg(-1) . min(-1)) increase d coronary sinus ET-1 levels similar to 50-fold, decreased coronary bl ood flow per unit of interstitial space by similar to 30% (P = 0.006), and increased myocardial microcirculatory transit times (n = 6). Perm eability to albumin was unaffected by ET-1, whereas the permeability-s urface area product for sucrose decreased following derecruitment of m yocardial capillaries. We conclude that there is a normal myocardial m etabolic balance of ET-1 and that the heart marginally contributes to circulating ET-1. Pharmacological doses of ET-1 may adversely affect m yocardial metabolism by reducing blood flow and the permeability-surfa ce area product for small circulating substances.