Abolished tubuloglomerular feedback and increased plasma renin in adenosine A1 receptor-deficient mice

The hypothesis that adenosine acting on adenosine A(1) receptors (A(1)R) regulates several renal functions and mediates tubuloglomerular feedback (TGF) was examined using A(1)R knockout mice. We anesthetized knockout, wild-type, and heterozygous mice and measured glomerular filtration rate, TGF response using the stop-flow pressure (Psf) technique, and plasma renin concentration. The A(1)R knockout mice had an increased blood pressure compared with wild-type and heterozygote mice. Glomerular filtration rate was similar in all genotypes. Proximal tubular P-sf was decreased from 36.7 +/- 1.2 to 25.3 +/- 1.6 mmHg in the A(1)R+/+ mice and from 38.1 +/- 1.0 to 27.4 +/- 1.1 mmHg in A(1)R+/- mice in response to an increase in tubular flow rate from 0 to 35 nl/min. This response was abolished in the homozygous A(1)R-/- mice (from 39.1 +/- 4.1 to 39.2 +/- 4.5 mmHg). Plasma renin activity was significantly greater in the A(1)R knockout mice [74.2 +/- 14.3 milli-Goldblatt units (mGU)/ml] mice compared with the wild-type and A(1)R+/- mice (36.3 +/- 8.5 and 34.1 +/- 9.6 mGU/ml), respectively. The results demonstrate that adenosine acting on A(1)R is required for TGF and modulates renin release.