Abstract
It has been suggested that cyclic AMP (c-AMP) and cyclic GMP (c-GMP) are biologic effectors involved in regulating cellular functions that are controlled bidirectionally. In the control of vascular smooth muscle tone, cyclic nucleotides may act in a reciprocal manner with increases in c-AMP promoting relaxation and increases in c-GMP promoting contraction. But most of studies have been carried out in vitro. In order to elucidate the role of c-AMP and c-GMP in coronary vasodilation in vivo, the concentration of c-AMP and c-GMP in the conary artery and left ventricular muscle of anesthetized dogs were measured after the administration of various coronary vasodilators. Materials and Methods Seventy mongrel dogs weighing 9 to 11 kg were anesthetized with sodium thiamylal (25 to 30 mg/kg I.V), intubated and ventilated with a Harvard respirator. The chest was opened on the left side between the 4th and 5th ribs and the pericardium was opened. After 30 min control period, coronary vasodilators, which were papaverine (4 mg/kg), dipyridamole (0.5 mg/kg), nitroglycerin (0.02 mg/kg), isosorbide dinitrate (0.3 mg/kg), amyl nitrite (0.25 ml), nifedipine (5 μg/kg), and diltiazem (0.2 mg/kg) were administered intravenously except for amyl nitrite. We performed a method of catheterization of the coronary sinus as means of measurement of coronary blood flow. The blood flow. The blood from the coronary sinus was returned to the external jugular vein and a electromagnetic flowmeter (Nihon-Koden MF-2) was setted between the coronary sinus and the external jugular vein. When coronary blood flow was at its maximum, the heart was removed and immediately irradiated for 2 min with microwave (2450 MHz, 600W) for inactivation of the enzymes. The coronary artery and the left ventricular muscle were removed from the heart and weighed in cold room at 4°C. Tissue samples were homogenized in 1 ml of 6% trichloroacetic acid. C-AMP and c-GMP were measured by a modified radioimmunoassay of Cailla. Ethyl alcohol was administered in control group of nitroglycerin and nifedipine and distilled water was administered in the other control group. Mean and standard error of the mean were calculated and the data were compared by Student's unpaired t test. P values of less than 0.05 were considered significant.
