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

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Abstract
The hypothesis that adenosine acting on adenosine A1 receptors (A1R) regulates several renal functions and mediates tubuloglomerular feedback (TGF) was examined using A1R 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 A1R knockout mice had an increased blood pressure compared with wild-type and heterozygote mice. Glomerular filtration rate was similar in all genotypes. Proximal tubular Psf was decreased from 36.7 ± 1.2 to 25.3 ± 1.6 mmHg in the A1R+/+ mice and from 38.1 ± 1.0 to 27.4 ± 1.1 mmHg in A1R+/− mice in response to an increase in tubular flow rate from 0 to 35 nl/min. This response was abolished in the homozygous A1R−/− mice (from 39.1 ± 4.1 to 39.2 ± 4.5 mmHg). Plasma renin activity was significantly greater in the A1R knockout mice [74.2 ± 14.3 milli-Goldblatt units (mGU)/ml] mice compared with the wild-type and A1R+/− mice (36.3 ± 8.5 and 34.1 ± 9.6 mGU/ml), respectively. The results demonstrate that adenosine acting on A1R is required for TGF and modulates renin release.