Influence of the adenosine A1 receptor on blood pressure regulation and renin release.
The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) 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 A1R-/- than in A1R+/+ mice. HS diet did not affect the MAP in A1R-/- mice, but the daytime and nighttime MAP of the A1R+/+ mice increased by approximately 10 mmHg, to the same level as that in the A1R-/-. On the SD diet, day- and nighttime MAP decreased by approximately 6 mmHg in both A1R-/- and A1R+/+ mice, although the MAP remained higher in A1R-/- than in A1R+/+ mice. Although plasma renin levels decreased with increased salt intake in both genotypes, the A1R-/- mice had an approximately twofold higher plasma renin concentration on all diets compared with A1R+/+ mice. Sodium excretion was elevated in the A1R-/- compared with the A1R+/+ 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, A1R-/- mice had an increased sodium excretion compared with A1R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A1R-/- animals. The elevated plasma renin concentrations found in the A1R-/- 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.
Brown
Russell D
RD
Dept. of Medical Cell Biology, Division of Integrative Physiology, Uppsala Univ., S-751 23 Uppsala, Sweden.
Thorén
Peter
P
Steege
Andreas
A
Mrowka
Ralf
R
Sällström
Johan
J
Skøtt
Ole
O
Fredholm
Bertil B
BB
Persson
A Erik G
AE
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004032:Diet; D004039:Diet, Sodium-Restricted; D004231:Diuresis / Q000187:drug effects; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000097:blood / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013686:Telemetry; D014563:Urodynamics; D014882:Water-Electrolyte Balance / Q000502:physiology
D043682:Receptor, Adenosine A1; D017673:Sodium Chloride, Dietary; D012083:Renin