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A novel mechanism of renal blood flow autoregulation and the autoregulatory role of A₁ adenosine receptors in mice

¹Department of Cell and Molecular Physiology, ²Carolina Cardiovascular Biology Center, ³University of North Carolina Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Submitted 31 May 2007 ; accepted in final form 27 August 2007

Autoregulation of renal blood flow (RBF) is mediated by a fast myogenic response (MR; 5 s), a slower tubuloglomerular feedback (TGF; 25 s), and potentially additional mechanisms. A₁ adenosine receptors (A1AR) mediate TGF in superficial nephrons and contribute to overall autoregulation, but the impact on the other autoregulatory mechanisms is unknown. We studied dynamic autoregulatory responses of RBF to rapid step increases of renal artery pressure in mice. MR was estimated from autoregulation within the first 5 s, TGF from that at 5–25 s, and a third mechanism from 25–100 s. Genetic deficiency of A1AR (A1AR–/–) reduced autoregulation at 5–25 s by 50%, indicating a residual fourth mechanism resembling TGF kinetics but independent of A1AR. MR and third mechanism were unaltered in A1AR–/–. Autoregulation in A1AR–/– was faster at 5–25 than at 25–100 s suggesting two separate mechanisms. Furosemide in wild-type mice (WT) eliminated the third mechanism and enhanced MR, indicating TGF-MR interaction. In A1AR–/–, furosemide did not further impair autoregulation at 5–25 s, but eliminated the third mechanism and enhanced MR. The resulting time course was the same as during furosemide in WT, indicating that A1AR do not affect autoregulation during furosemide inhibition of TGF. We conclude that at least one novel mechanism complements MR and TGF in RBF autoregulation, that is slower than MR and TGF and sensitive to furosemide, but not mediated by A1AR. A fourth mechanism with kinetics similar to TGF but independent of A1AR and furosemide might also contribute. A1AR mediate classical TGF but not TGF-MR interaction.

renal hemodynamics; tubuloglomerular feedback; kidney myogenic response; afferent arteriole; macula densa