LONG-LASTING CORONARY VASOCONSTRICTOR EFFECTS AND MYOCARDIAL UPTAKE OF ENDOTHELIN-1 IN HUMANS

The effect of intravenous administration of the endothelium-derived va soconstrictor peptide endothelin-1 (ET-1 0.2. 1 and 8 pmol kg(-1) min( -1)) on coronary blood flow in relation to plasma ET-1 as well as bloo d lactate and glucose levels were investigated in six healthy voluntee rs. Coronary sinus blood flow was measured by thermodilution. Administ ration oi ET-1 elevated arterial plasma ET 35-fold, dose-dependently i ncreased mean arterial blood pressure from 95 +/- 5 mmHg to 110 +/- 6 mmHg (P < 0.01) and reduced heart rate from 64 +/- 4 beats min(-1) to 58 +/- 4 beats min(-1) (P < 0.05) at 8 pmol kg(-1) min(-1). Coronary s inus blood flow was reduced maximally by 23 +/- 4% (P < 0.01) and coro nary vascular resistance increased by 48 +/- 11% (P < 0.01). Coronary sinus oxygen saturation decreased from 35 +/- 1% to 22 +/- 2% at 2 min after the infusion (P < 0.01). A coronary constrictor response was ob served at a 4-fold elevation in plasma ET. The reduction in coronary s inus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lacta te net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal oi plasma ET by 2 4 +/- 3% over the myocardium (P < 0.05). The results show that ET-1 in duces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-f old elevation in plasma ET-1. Furthermore, there is a net removal of c irculating ET-1 by the myocardium.