Vascular Reactivity by Purinoceptor Activation in Rat Inferior Vena Cava

ABSTRACT

BACKGROUND: Extracellular ATP, released from platelets and nerve endings, plays significant roles in the regulation of circulation. The effects of ATP depend on the location of the vessels and the species of experimental animals. Until now, studies were limited to arteries, so we compared the effects of ATP in rat vena cava with those in the aorta and attempted to identify the characteristics of their receptors. METHODS: Vascular rings were isolated from the rat inferior vena cava and descending thoracic aorta. Endothelial cells were preserved or removed by gentle rubbing. The isometric contractions were recorded on polygraph using a force transducer. RESULTS: In the vena cava ring precontracted by 100 nM norepinephrine (NE), ATP elicited relaxations in a dose-dependent manner. These effects were abolished by removal of the endothelium or pretreatment with a nitric oxide synthase inhibitor. Relaxations to ATP in the vena cava (EC509.9 microM) were less potent than those in the aorta (1.7 microM). The relative order of potencies was ADP>ATP>AMP>adenosine, but the maximal relaxation to ADP was smaller than to ATP. ATP-induced vasorelaxation was blocked by suramin, a nonselective antagonist for P2 purinoceptor and reactive blue-2, a P2Y blocker. At basal tension, ATP contracted the vena cava dose-dependently and these effects were potentiated by endothelium-removal. Contractions in the vena cava were also less potent than in the aorta, and the order of potencies was alpha, beta-MeATP>UTP>ATP>ADP>AMP=adenosine. ATP-induced vasoconstriction was blocked by suramin and alpha, beta-MeATP, a desensitizing antagonist of P2X purinoceptor, and potentiated by pretreatment with UTP. CONCLUSION: These results suggest that ADP and ATP acts on P2Y1- and P2Y2-purinoceptor in the endothelium, respectively and induces vasorelaxation of the vena cava, which is mediated by nitric oxide. Since ATP and UTP induced vasoconstriction in endothelium-denuded condition, it may be mediated by the activation of the P2X and P2Y4, 6 purinoceptor on smooth muscles, respectively.