Vasomotor effects of purinergic agonists in isolated rabbit afferent arterioles

Abstract

To examine the vasomotor effects of purinergic agonists, experiments were performed in isolated afferent arterioles of rabbit kidneys dissected together with their glomerulus and perfused with a pressure head of 120 cmH2O. Changes in vascular diameter were taken as measure of changes in vasomotor tone. Adenosine caused a dose-dependent and persistent decrease in vascular diameter along the entire afferent arteriole with significant changes being detectable at 10(-8) M. Constrictor effects were more pronounced in the glomerular entrance segment of the arteriole where adenosine caused a progressive diameter reduction with maximum contraction at 10(-4) M. Similar monophasic diameter reductions of the distal afferent arteriole were seen with increasing bath concentrations of 2-chloroadenosine (2-ClAdo), cyclohexyladenosine (CHA), and 5'-(N-ethylcarboxamido)adenosine (NECA). Concentrations to achieve half-maximum responses were 92.5 nM for 2-ClAdo, 39 nM for CHA, and 107 nM for NECA. The A2-receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine had no effect on vessel diameter. Increasing bath concentrations of ATP caused significant diameter reductions in both the proximal and distal parts of the afferent arterioles. Addition of the A1-receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine, eliminated the effect of ATP in the proximal region of the arteriole, but a significant diameter reduction was still seen in the glomerular entrance segment. The ATP analogue, beta gamma-methylene-ATP, caused a significant diameter reduction in this segment. These results are consistent with an essentially exclusive presence of A1 receptors in the glomerular entrance segment of the afferent arteriole, whereas in more proximal regions A2 receptors appear to also be expressed in low density. These studies also provide functional evidence for the presence of P2x receptors in renal afferent arterioles.