Characterization of the Vascular Phenotype of the Equilibrative Nucleoside Transporter 1 Knockout Mouse

Abstract

Adenosine is important in the endogenous regulation of vascular tone. Equilibrative Nucleoside Transporter 1 (ENT1) is an established regulator of adenosine concentrations in vascular tissues. Thus, changes in ENT1 expression and/or activity may alter vascular tone regulation. We therefore examined the cardiovascular phenotype of ENT1‐knockout (KO) mice as compared to wild type (WT) mice. Heart rates and blood pressures of KO and WT littermate male mice were obtained. Vascular reactivity was assessed in aortic ring segments obtained from 3 and 6 month old KO and WT mice. KCl‐induced depolarization led to significantly greater constriction (~32% increase independent of tension applied or age) in KO rings compared to WT. However, no significant differences between the two genotypes were observed using a series of receptor‐selective constrictors. Morphological assessment of H&E stained vascularized tissues yielded no significant difference in luminal area or arterial wall thickness between WT and KO mice at the age of 3 months. The enhanced effect of KCl in KO aortic rings suggests a physiological difference in the regulation of depolarization‐induced, but not receptor‐mediated, vasoconstriction response in aorta. Further assessment of this model will aid in our understanding of the role of adenosine in vascular regulation.