Contrasting effects of changes in salt balance on the renovascular response to A1-adenosine receptor stimulation in vivo and in vitro in the rat.
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.
Nies
A S
AS
Department of Pharmacology, University of Colorado School of Medicine, Denver.
Beckmann
M L
ML
Gerber
J G
JG
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D012965:Sodium Chloride / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
D011983:Receptors, Purinergic; C027513:N(6)-cyclohexyladenosine; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D000241:Adenosine