Adenosine as a mediator of macula densa-dependent inhibition of renin secretion.

Adenosine acting through A1 adenosine receptors (A1AR) has been shown previously to be required for the vasoconstriction elicited by high luminal NaCl concentrations at the macula densa (MD). The present experiments were performed to investigate a possible role of A1AR in MD control of renin secretion in conscious wild-type (WT) and A1AR-deficient mice. The intravenous injection of NaCl (5% body wt) reduced plasma renin concentration (PRC; ng ANG I·ml−1·h−1) from 1,479 ± 129 to 711 ± 77 (P < 0.0001; n = 18) in WT mice but did not significantly change PRC in A1AR−/− mice (1,352 ± 168 during control vs. 1,744 ± 294 following NaCl; P = 0.19; n = 17). NaCl injections also caused a significant reduction in PRC in β1/β2-adrenergic receptor−/− mice (298 ± 47 vs. 183 ± 42; P = 0.03; n = 6). Injections of isotonic NaHCO3 (5% body wt) elicited significant increases in PRC in both WT and A1AR−/− mice. NaCl as well as NaHCO3 injections were accompanied by transient increases in blood pressure, heart rate, and activit...