Abolished tubuloglomerular feedback and increased plasma renin in adenosine A(1) receptor-deficient mice

The hypothesis that adenosine acting on adenosine A(1) receptors (A(1)R) re gulates several renal functions and mediates tubuloglomerular feedback (TGF ) was examined using A(1)R knockout mice. We anesthetized knockout, wild-ty pe, and heterozygous mice and measured glomerular filtration rate, TGF resp onse using the stop-flow pressure (Psf) technique, and plasma renin concent ration. The A(1)R knockout mice had an increased blood pressure compared wi th 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 fro m 0 to 35 nl/min. This response was abolished in the homozygous A(1)R-/- mi ce (from 39.1 +/- 4.1 to 39.2 +/- 4.5 mmHg). Plasma renin activity was sign ificantly 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.