Cyclic GMP-dependent relaxation of isolated rat renal glomeruli induced by extracellular ATP

摘要

class="enumerated" style="list-style-type:decimal">The relaxing effect of extracellular ATP on renal glomeruli has been investigated by applying ATP and its analogues to suspensions of angiotensin II-precontracted rat renal glomeruli. Based on changes of glomerular [³H]inulin space (GIS) the relaxation of glomeruli was analysed in the presence of agonists: ATP, ADP, AMP, UTP, 2-methylthio-ATP (P2Y agonist), β,γ-methylene-ATP (P2X agonist) and adenosine.ATP, 2-methylthio-ATP, ADP and UTP induced concentration-dependent relaxation whereas AMP, β,γ-methylene-ATP and adenosine had no effect. The rank order of relaxation potency was 2-methylthio-ATP > ATP > ADP > UTP.An inhibitor of constitutive nitric oxide synthase (NOS), N^ω-nitro-L-arginine (NNA) prevented the ATP-induced increased accumulation of L-citrulline and the relaxation effect of ATP. An inhibitor of the neuronal isoform of NOS, 7-nitroindazole, had no effect on the relaxation effect of ATP.The relaxing effect of ATP was prevented in the presence of inhibitors of cyclic guanylyl cyclase: methylene blue (MB) and the more specific inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ). ATP stimulated an accumulation of cGMP that was diminished in the presence of MB.We indicated that extracellular ATP may relax the glomeruli via activation of P2Y receptors with the subsequent activation of the endothelial isoform of nitric oxide synthase and soluble guanylyl cyclase. We suggest that, based on the described mechanism, extracellular ATP may increase the filtration surface which, in turn, may influence the glomerular filtration rate.