Abstract

Stimulation of renal A1-adenosine receptors produces vasoconstriction that is maximal when the animal is salt-depleted and is inhibited during salt loading. We postulated that the effect of salt balance on the vasoconstrictor response to A1-adenosine receptor stimulation was due to a change intrinsic to the kidney, perhaps related to a change in responsiveness of the renal A1-adenosine receptor population. We tested this hypothesis by determining the renovascular response to the metabolically stable, selective, A1-adenosine receptor agonist N6-cyclohexyladenosine (CHA) in salt-loaded and salt-depleted rats in vivo and in isolated, perfused kidneys harvested from these rats. CHA was a renal vasoconstrictor in the salt-depleted animals and a renal vasodilator in the salt-loaded rats. In the isolated, perfused kidneys, CHA produced a biphasic response with submicromolar concentrations being vasoconstrictor and higher concentrations being vasodilator. In contrast to the response in vivo CHA was a more potent vasoconstrictor in the isolated, perfused kidneys that had been removed from salt-loaded animals. Indomethacin enhanced the vasoconstrictor response to CHA in the kidneys removed from salt-loaded animals but had no effect on the kidneys from salt-depleted animals. These findings indicate that the inhibition of the renal vasoconstrictor response to CHA in salt-loaded animals is not related to a change within the kidney but that a factor extrinsic to the kidney must be responsible for the change in adenosine responsiveness in vivo.