Endothelin does not interact with angiotensin II in the coronary vascular bed of anesthetized dogs

We postulated that individually subthreshold circulating levels of angiotension II (Ang II) and endothelin-1 (ET-1) might induce fulminant coronary vasoconstriction when both are present. In 16 pentobarbital-anesthetized, open-chest mongrel dogs, blood pressure, heart rate, and standard ECG were registered continuously. Coronary blood flow (CBF) was measured in the left anterior descending coronary artery (LAD) by an electromagnetic flow probe. Drugs were administered into the LAD via an indwelling catheter. Bolus injections of Ang II (7.8 x 10(-13) to 3.9 x 10(-11) M) and ET-1 (10(-12) to 10(-9) M) induced a dose-dependent decrease in CBF (delta CBFmax -82 +/- 10% for Ang II and -91 +/- 8% for ET-1). Simultaneous Ang II and ET-1 boluses had slightly smaller effects on CBF than the calculated additive figure. Five-minute infusions of Ang II (10(-12) to 10(-10) M/min) and ET-1 (5 x 10(-12) to 2 x 10(-10) M/min) induced a slight decrease in CBF (delta CBFmax -12 +/- 9% for Ang II and -19 +/- 9% for ET). Background ET-1 or Ang II infusions did not alter the dose-response curve of the other drug. Simultaneous Ang II and ET-1 infusions at different rates (10(-12) to 10(-10) M/min for Ang II and 5 x 10(-12) to 2 x 10(-10) M/min for ET-1) over 5 min had similar effects on CBF as the calculated additive figure (delta CBFmax -35 +/- 17% for the joint administration of the highest doses). We conclude that after simultaneous administration into the dog coronary artery, Ang II and ET-1 do not interact sufficiently to induce fulminant vasoconstriction.