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(Hypertension. 2005;46:780.)
© 2005 American Heart Association, Inc.

Original Articles

Blood Pressure–Dependent Inhibition of Renin Secretion Requires A1 Adenosine Receptors

Frank Schweda; Florian Segerer; Hayo Castrop; Jürgen Schnermann; Armin Kurtz

From the Institute of Physiology (F. Schweda, F. Segerer, H.C., A.K.), University of Regensburg, Germany; and National Institutes of Health (J.S.), National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md.

Correspondence to Frank Schweda, MD, Institute of Physiology, University of Regensburg, 93040 Regensburg, Germany. E-mail frank.schweda{at}klinik.uni-regensburg.de

Renal perfusion pressure (RPP) regulates renin release with a reduction of RPP stimulating and an elevation inhibiting renin secretion. The precise sensing and effector mechanisms by which changes in arterial pressure are linked to the exocytosis of renin are not well-defined. The present experiments were designed to study the potential role of adenosine as a mediator of this renal baroreceptor mechanism. In isolated perfused mouse kidneys a stepwise reduction of RPP from 90 mm Hg to 65 and 40 mm Hg stimulated renin secretion rates (RSR) 1.4-fold and 3.6-fold, whereas stepwise elevations of RPP from 90 mm Hg to 115 and 140mm Hg suppressed RSR to 64% or 40% of baseline. Inactivation of A1 adenosine receptors by either pharmacological blockade (DPCPX 1µmol/L) or genetic deletion (A1AR^–/– mice) did not modify the stimulation of renin release by a low RPP, but completely prevented the suppression of renin secretion by higher perfusion pressures. In vivo, the induction of arterial hypertension by either acute (single subcutaneous injection) or chronic (osmotic minipump for 72 hours) application of phenylephrine significantly reduced plasma renin concentration (PRC) in wild-type mice to 40% of control, whereas it did not significantly affect PRC in A1AR^–/– mice. Together these data demonstrate that A1 adenosine receptors are indispensable for the inhibition of renin secretion by an increase in blood pressure, suggesting that formation and action of adenosine is responsible for baroreceptor-mediated inhibition of renin release. In contrast, the stimulation of the renin system by a low blood pressure appears to follow different pathways.

Key Words: kidney • phenylephrine • prostaglandins

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