Our previous data indicated that various subtypes of connexin (Cx) were expressed in the juxtaglomerular apparatus. Experiments were performed to characterize the effects on renal autoregulation of specific mimetic peptides that inhibit these Cx subtypes in Wistar Kyoto rats. Intra-renal infusion of ^Cx37,43GAP27 increased autoregulatory index of renal plasma flow (RPF, 0.06±0.05 to 0.47±0.06, n=6, p<0.05) and glomerular filtration rate (GFR, 0.01±0.07 to 0.49±0.07, p<0.05). The additional administration of 8-cyclopentyl- 1,3-dipropylxanthine (CPX) produced a further elevation of autoregulatory index of RPF (0.86±0.07, p<0.05) and GFR (0.88±0.09, p<0.05), compared to ^Cx37,43GAP27 alone. However, addition of pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid (PPADS) to ^Cx37,43GAP27 did not. Combined treatment with CPX and PPADS markedly worsened autoregulatory index of RPF (0.04±0.10 to 0.81±0.06, n=6 p<0.01) and GFR (0.05±0.08 to 0.79±0.05, p<0.01). ^Cx40GAP27 induced similar changes to ^Cx37,43GAP27. Renal autoregulation was preserved in the presence of ^Cx43GAP26. Our results indicate that the inhibition of gap junction impaired renal autoregulation. Furthermore, the present data provide evidence that both adenosine and purinergic receptors contribute to glomerular autoregulation. Finally, our findings suggest that gap junctions at least in part transduce purinergic signals mediating renal autoregulation.