In vivo effects of diadenosine polyphosphates on rat renal microcirculation

Background. Diadenosine polyphosphates (APXA) are vasoactive nucleotides th at elicit effects via purinoceptors. Recent data suggest differential effec ts of APXA on kidney vasculature. Methods. The in vivo effects of AP3A, AP5A, and adenosine on renal microves sels and the role of purinoceptors were investigated by the application of agonists to the hydronephrotic rat kidney and preincubation with respective antagonists. Results. The addition of the agonists (10(-7) mol/L up to 10(-4) mol/L) res ulted in a concentration-dependent transient vasoconstriction [interlobular artery (ILOB): adenosine 30 +/- 7%, N = 7, AP3A 35 +/- 10%, N = 5; AP5A 66 +/- 19%, N = 5; 10(-5) mol/L each] lasting up to one minute, followed by a concentration-dependent vasodilation (ILOB: adenosine 10 +/- 3%, N = 6; AP 3A 19 +/- 4%, N = 5; AP5A 12 +/- 5%, N = 6; 10-5 mol/L each). In ILOB and i n the afferent arteriole (AFF), the constrictory effects of AP5A were more pronounced than those of AP3A and adenosine. In the efferent arteriole (EFF ), vascular tone was only slightly affected by all agonists. The dilatory p otency was comparable for all agonists in ILOB and EFF. No significant vaso dilation occurred in AFF. The application of the selective A(1) receptor an tagonist DPCPX (10(-5) mol/L) completely abolished the adenosine-induced va soconstriction, whereas the A, receptor antagonist DMPX and the P2 purinoce ptor antagonists PPADS and A3P5P (all 10(-5) mol/L) did not affect adenosin e-induced constriction. The AP3A-induced constriction was abolished by DPCP X and was partially inhibited by PPADS. The constriction induced by AP5A wa s less sensitive to DPCPX but more sensitive to PPADS. In ILOB and EFF, DMP X or A3P5P abolished dilation after the addition of the agonists. The dilat ion after AP5A was not significantly reduced. In AFF, no significant dilati on was observed with these agonists alone, but it was clearly visible in th e presence of DPCPX or PPADS. Conclusions. APXA evoke transient constrictions in vessels of the hydroneph rotic rat kidney, which are mediated by A(1) and P2 purinoceptors. The leng th of the phosphate chain determines the degree of vasoconstriction and the extent to which the substances exert effects on the P2 purinoceptor subtyp es. ILOB and AFF are more potently affected by APXA than EFF. Afferent vaso dilation is partially overridden by sustained vasoconstriction.