Influence of the adenosine A1 receptor on blood pressure regulation and renin release

The present study was performed to investigate the role of adenosine A(1) receptors in regulating blood pressure in conscious mice. Adenosine A(1)-receptor knockout (A(1)R-/-) mice and their wild-type (A(1)R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD) diets for a minimum of 10 days before telemetric blood pressure and urinary excretion measurements in metabolic cages. On the NS diet, daytime and nighttime mean arterial blood pressure (MAP) was 7 - 10 mmHg higher in A(1)R-/- than in A(1)R+/+ mice. HS diet did not affect the MAP in A(1)R-/- mice, but the daytime and nighttime MAP of the A(1)R+/+ mice increased by similar to 10 mmHg, to the same level as that in the A(1)R-/-. On the SD diet, day- and nighttime MAP decreased by similar to 6 mmHg in both A(1)R-/- and A(1)R+/+ mice, although the MAP remained higher in A(1)R-/- than in A(1)R+/+ mice. Although plasma renin levels decreased with increased salt intake in both genotypes, the A(1)R-/- mice had an approximately twofold higher plasma renin concentration on all diets compared with A(1)R+/+ mice. Sodium excretion was elevated in the A(1)R-/- compared with the A(1)R+/+ mice on the NS diet. There was no difference in sodium excretion between the two genotypes on the HS diet. Even on the SD diet, A(1)R-/- mice had an increased sodium excretion compared with A(1)R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A(1)R-/- animals. The elevated plasma renin concentrations found in the A(1)R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion.