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1 Institut für Physiologie and 2 Klinik und Poliklinik für Innere Medizin, Universität Regensburg, 93040 Regensburg, Germany; and 3 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Recent studies demonstrated that
the influence of the macula densa on glomerular filtration is abolished
in adenosine A1 receptor (A1AR) knockout mice.
Inasmuch as the macula densa not only regulates glomerular filtration
but also controls the activity of the renin system, the present study
aimed to determine the role of the A1AR in macula densa
control of renin synthesis and secretion. Although a high-salt diet
over 1 wk suppressed renin mRNA expression and renal renin content to
similar degrees in A1AR+/+,
A1AR+/
, and A1AR/
mice, stimulation of Ren-1 mRNA expression and renal renin
content by salt restriction was markedly enhanced in
A1AR/ compared with wild-type mice.
Pharmacological blockade of macula densa salt transport with loop
diuretics stimulated renin expression in vivo (treatment with
furosemide at 1.2 mg/day for 6 days) and renin secretion in
isolated perfused mouse kidneys (treatment with 100 µM bumetanide) in
all three genotypes to the same extent. Taken together, our data are
consistent with the concept of a tonic inhibitory role of the
A1AR in the renin system, whereas they indicate
that the A1AR is not indispensable in macula
densa control of the renin system.
loop diuretics; low salt; high salt
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