Preserved macula densa-dependent renin secretion in A1 adenosine receptor knockout mice

Abstract

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.