Further characterization of the renovascular effects of N6-cyclohexyladenosine in the isolated perfused rat kidney.
Previous studies have shown that activation of A1 adenosine receptors results in renal vasoconstriction at submicromolar concentrations of N6-cyclohexyladenosine (CHA) followed by relative vasodilation at higher concentrations. The present data confirm these findings and demonstrate that Na loading enhances the vasoconstrictor effects of CHA in the isolated rat kidney perfused at constant flow. Furthermore, adenosine receptor antagonism with both theophylline and the A1-selective antagonist, xanthine amine congener (8-[4-[(2-aminoethyl)-aminocarbonylmethyloxy]phenyl]-1, 3-dipropylxanthine), produced a rightward and apparently parallel shift in the dose response to CHA. Determination of the inhibitory constants for both antagonists revealed that xanthine amine congener was three orders of magnitude more potent than theophylline in antagonizing CHA-induced renal vasoconstriction. Other investigators have hypothesized that angiotensin II mediates adenosine-induced renal vasoconstriction. However, we have been able to show that A1 receptor activation can result in renal vasoconstriction in the isolated perfused rat kidney devoid of renin substrate. Moreover, a competitive inhibitor of angiotensin II (saralasin) failed to attenuate the hemodynamic effects of CHA at doses that completely blocked the effects of angiotensin II itself. Taken together, these data are consistent with the hypothesis that A1 receptor activation in the kidney leads to vasoconstriction, a response that is enhanced by Na loading, and that A1 adenosine receptors and angiotensin II receptors are separate and distinct biochemical entities. Independent activation of either receptor leads to renal vasoconstriction, which can be prevented by its respective antagonist.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D007668:Kidney / Q000502:physiology; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; C051869:8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine; D013806:Theophylline; D000241:Adenosine