Systemic and coronary hemodynamic effects of JTV-506, a novel potassium channel opener, in conscious dogs: Comparison with cromakalim and nicorandil

We compared the coronary and systemic hemodynamic effects of JTV-506, a nov el potassium channel opener, with those of cromakalim and nicorandil in chr onically instrumented conscious dogs. Experiments were performed in 7 dogs which had undergone the implantation of flow probes on the ascending aorta and left circumflex coronary artery, and of catheters into the descending t horacic aorta and left ventricular cavity, respectively. On different days at least 10 days after the implantation, dogs were randomly assigned to the doses of JTV-506 (2, 5 or 10 mu g/kg), cromakalim (10 mu g/kg), nicorandil (0.2 mg/kg) or glibenclamide (5 mg/kg) plus JTV-506 (5 mu g/kg). Each dose of the three drugs produced dose-related increases in heart rate, coronary blood flow, cardiac output, dP/dt(max) and %SS, and produced decreases in arterial blood pressure, left ventricular systolic pressure, and coronary a nd systemic vascular resistance. JTV-506 at doses of 2. and 5 mu g/kg reduc ed arterial blood pressure only slightly as compared to its significant cor onary vasodilating effect. An increase in myocardial oxygen consumption (as estimated by pressure-work index) was also observed in response to each do se of three drugs. At doses that reduced coronary vascular resistance by 75 %, JTV-506 produced a greater increase in coronary blood flow, as compared with cromakalim and nicorandil. JTV-506 has the longest duration of action as compared with cromakalim and nicorandil. Glibenclamide pretreatment comp letely abolished the effects of JTV-506 on coronary and systemic hemodynami cs. These results suggest that JTV-506 is relatively more potent in the cor onary bed with minimal systemic influence, and exerts a longer time course of action.