Angina is a chest pain due to the transient myocardial ischemia that often occurs in patients of various ischemic heart diseases. Myocardial ischemia activates afferent sympathetic nerves. These afferent signals are relayed in the brain regions that regulate cardiovascular functions. Efferent commands issued from these brain regions may then stimulate the sympathetic nervous systems. By increasing the heart rate and the blood pressure, the myocardial ischemia-induced sympathetic excitatory reflex may increase the work load of the heart, cause myocardial hypoxia, and worsen angina. KATP channel openers (KCOs) can relax coronary arteries and is often used to treat hypertension and angina. This thesis aimed to elucidate the roles of KCOs in suppression of central sympathetic outflow. Pharmacological tests were conducted in two experimental models. First, spontaneous sympathetic nerve discharges (SND) were recorded from in vitro splanchnic sympathetic nerve–thoracic spinal cord preparations of neonatal Sprague-Dawley rats. By bath applications of various agents, the effects of activation or inactivation of ATP-sensitive potassium (KATP) channels on SND were examined. Second, systemic arterial blood pressure (SABP) was measured in anesthetized adult rats. The blood pressure low frequency components (BLF) were obtained from power spectral analysis of SABP fluctuations. BLF was taken as an index of the sympathetic outflow regulating vasomotor activities. Various agents that affect KATP channel activities in the spinal cord were applied by intrathecal injections. The data obtained from in vitro and in vivo experiments were compared. Under in vitro experimental conditions, applications of P1075 or nicorandil to activate KATP channels increased, decreased, or did not change SND. In contrast, applications of diazoxide to activate KATP channels consistently decreased SND. Pre-treatment of glyburide (KATP channel blocker) or L-NAME (nitric oxide synthase inhibitor) attenuated the effects elicited by applications of nicorandil. Taken together, these findings in combination with the evidence provided by the other laboratories corroborate the notion that the nicorandil effects on SND are derived from activation of NO/KATP pathway. On the other hand, under in vivo experimental conditions, intrathecal injection of nicorandil or diazoxide had little effect on blood pressure but could increase or decrease BLF. Intrathecal injection of P1075 consistently decreased blood pressure, increased heart rate, and reduced BLF. Because endothelial KATP channels may be more sensitive to P1075 than diazoxide whereas neuronal KATP channels is more sensitive to diazoxide, part of P1075-induced BLF changes may be explained by its effects on vascular KATP channels, which lead to a decrease of blood pressure. In summary, the findings here support a central role of KATP channels in sympathetic regulation. It is very important and helpful for clinicians to realize these drug effects on blood pressure, heart rate, and sympathetic nerve system. This work gives doctor more clues to diagnose and to treat those complications combined with coronary artery diseases.