Bidirectional Regulatory Effects of Dexmedetomidine on Porcine Coronary Tone In Vitro

BACKGROUND Studies in vivo have shown that dexmedetomidine (DEX) could protect the myocardium and modulate the coronary blood flow. This study aimed to investigate the direct and concentration-dependent effects of DEX on the tone of porcine coronary artery in vitro and the underlying mechanisms. MATERIAL AND METHODS Distal branches of the porcine anterior descending coronary arteries were dissected and cut into 3-5 mm rings. The tones of coronary rings in response to cumulative DEX were measured using the PowerLab system. Coronary rings were divided into three groups: 1) endothelium-intact coronary rings without drug pretreatment (control); 2) endothelium-intact coronary rings pretreated with either yohimbine, tetraethylamine (TEA) or NG-nitro-L-arginine methyl ester (L-NAME); and 3) endothelium-denuded coronary rings pretreated with either yohimbine or TEA. RESULTS DEX induced coronary ring relaxation at lower concentrations (10^-9 to 10^-7 M) followed by constriction at higher concentrations (10^-6 to 10^-5 M). The coronary constrictive effect of higher DEX (10^-5 M) was greater in the endothelium-denuded rings than in the endothelium-intact rings. Yohimbine reduced the coronary constrictive effect of DEX at higher concentrations (10^-6 to 10^-5 M). TEA and L-NAME significantly reduced the coronary relaxing effect of DEX at lower concentrations (10^-9 to 10^-7 M) in endothelium-intact rings. TEA attenuated the coronary relaxation induced by DEX in endothelium-denuded rings. CONCLUSIONS DEX exerts bidirectional effects on porcine coronary tone. The coronary relaxing effect of DEX at lower concentrations is likely associated with endothelium integrity, NO synthesis and BKCa channel activation, while the coronary constrictive effect of DEX at higher concentrations is mediated by a2 adrenoceptors in the coronary smooth muscle cells.