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

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 8 September 2005 ; accepted in final form 16 November 2005

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 ₁/₂-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 activity that were similar in WT and A1AR–/– mice. The increase in PRC caused by an intraperitoneal injection of furosemide (40 mg/kg) was comparable in WT and A1AR–/– mice, and it was accompanied by similar transient increases in blood pressure, heart rate, and activity. Similarly, the stimulation of PRC caused by hydralazine was the same in WT and A1AR–/– mice. We conclude that the inhibition of renin secretion in response to an increase in NaCl at the MD requires A1AR and therefore appears to be adenosine dependent, whereas the stimulation of renin secretion during reductions in MD NaCl transport or arterial pressure does not require functional A1AR.

A₁ adenosine receptor; ₁/₂-adrenergic receptor knockout; telemetry; furosemide; hydralazine; propranolol

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