Pharmacological Studies Of Endogenous And Exogenous Vasoactive Agents On Coronary Artery

Coronary artery plays an important role in cardiovascular diseases, and coronary artery is the key target organ in the research of cardiovascular pharmacology. This study was designed to evaluate the pharmacological properties of chrysin and caffeic acid phenethyl ester (CAPE), which are two constituents isolated from honeybee propolis, in porcine coronary artery in vitro in comparison with an endogenous neuropeptide r/m Hemokinin-1. The possible mechanisms that contribute to the vasodilatation in coronary artery of the three compounds are discussed. Furthermore, chrysin, as well as the extract of propolis, were proven to be effective in preventing heart angina in vivo.Propolis, or honeybee glue, is a natural product collected by honeybees from various sources of plants. Flavanoids (chrysin, luteolin, genistein, kaempherol, apigenin and tectochrysin) and the derivates (caffeic acid, ferulic acid, caffeic acid phenethyl ester) are constituents which are responsible for at least some of the biological activities of propolis. On isolated porcine coronary artery, both chrysin and caffeic acid phenethyl ester exerted marked vasodilator effect. The mechanisms of vasorelaxation mediated by the two compounds are different. Chrysin (as well as the ethanol extract of propolis, EEP) evoked an endothelium independent vasodilatation of porcine coronary artery rings in normal circumstance, but a partly endothelium dependent vasodilatation in high extracellular K⁺ concentration surroundings, which suggested that K⁺ channels on the membrane of vascular smooth muscle cells may contribute to chrysin-evoked vasodilatation; when the K⁺ channels are inhibited by high K⁺ concentration, endothelium-NO pathway is triggered to produce an compensatory vasorelaxation. The vasorelaxant property of caffeic acid phenethyl ester is partly endothelium dependent through activation ofβ-adrenoceptor, but not coupled with K⁺ channels.Rat and mouse hemokinin-1 (r/m hemokinin-1) is a recently described member of tachykinin family, r/m Hemokinin-1 evoked a marked endothelium-dependent vasodilatation of coronary arteries through activating endothelial tachykinin NK₁ receptors. Two components contributed to this r/m hemokinin-1 -elicited vasodilatation, the first of which is the endothelium-derived hyperpolarizing factor (EDHF) that played a major role. This EDHF was identified as K⁺ currents through certain kind of K⁺channels on endothelium cell membrane of porcine coronary arteries. No inhibitory effects by specific antagonists to Ca²⁺-activated K⁺ channels on r/m hemokinin-1-induced vasodilatation were obtained, different from that in substance P-induced vasodilatation. When the potassium ion efflux was impaired by high K⁺ concentration (30mM) or removal of K⁺ from surroundings, NO synthesis was triggered by r/m hemokinin-1 to produce an equivalent EDHF (K⁺)-independent vasorelaxation as a compensatory mechanism.In conclusion, chrysin and caffeic acid phenethyl ester relaxed coronary artery with multiple target sites and longer half-life, but without specific receptors. Therefore, chrysin and the ethanol extract of propolis were proven beneficial in preventing and mending heart angina in vivo. On the other side, r/m hemokinin-1 relaxed coronary artery through activation of specific membrane receptors of vascular endothelial cells, and this vasodilatation is transient. Another interesting point that should be addressed is the widely existence of compensatory vasorelaxation between vascular endothelium and vascular smooth muscle cells (by chrysin), or between different mediating pathways inside vascular endothelial cells (by r/m hemokinin-1), which is in need of further investigations.