Inhibition of leukotriene D4-induced coronary vasoconstriction by leukotriene antagonists in the anesthetized dog.

Anesthetized open-chest dogs were instrumented for the measurement of left circumflex coronary artery (LCX) blood flow and aortic blood flow, systemic arterial blood pressure, heart rate, lead II ECG, left ventricular end-diastolic pressure, left ventricular developed pressure and left ventricular positive and negative dP/dt to study the hemodynamic effects of leukotriene D4 (LTD4) and selective LTD4 antagonists on the coronary vasculature. Administration of LTD4 alone into the LCX (0.625-10 micrograms) produced a dose-dependent decrease in LCX blood flow, dP/dt and aortic blood flow and an increase in left ventricular end-diastolic pressure. Systemic arterial blood pressure, left ventricular developed pressure and heart rate were unchanged by LTD4. During i.v. infusions of the LTD4 antagonists, SK&F 102922 or FPL 55712 (1 mg/kg/min), the dose-dependent decreases in LCX flow, dP/dt and aortic blood flow were blocked whereas the increase in left ventricular end-diastolic pressure remained unchanged. The thromboxane A2 antagonist, SK&F 88046 (5 mg/kg + 0.1 mg/kg/min), which has been reported previously to block the coronary blood flow reducing action of LTC4, had no effect on the LCX blood flow responses to intracoronary LTD4. In a separate study, dogs instrumented in a similar manner were given bolus injections of arginine-vasopressin (1 microgram), the thromboxane A2 mimetic, U-46619 (10 micrograms), LTD4 (10 micrograms), angiotensin II (1 microgram) and prostaglandin F2 alpha (100 micrograms) directly into the LCX to provoke coronary vasoconstriction. SK&F 102922 and FPL 55712 selectively blocked the coronary vasoconstriction produced by LTD4, but had no effect on vasoconstriction produced by the other agonists.(ABSTRACT TRUNCATED AT 250 WORDS)