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 novel potassium channel opener, with those of cromakalim and nicorandil in chronically 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 thoracic 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 microg/kg), cromakalim (10 microg/kg), nicorandil (0.2 mg/kg) or glibenclamide (5 mg/kg) plus JTV-506 (5 microg/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 and systemic vascular resistance. JTV-506 at doses of 2 and 5 microg/kg reduced arterial blood pressure only slightly as compared to its significant coronary vasodilating effect. An increase in myocardial oxygen consumption (as estimated by pressure-work index) was also observed in response to each dose 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 completely abolished the effects of JTV-506 on coronary and systemic hemodynamics. These results suggest that JTV-506 is relatively more potent in the coronary bed with minimal systemic influence, and exerts a longer time course of action.