Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus.
Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath. Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M) in the bathing solution and in vehicle control experiments. The control response to increasing luminal NaCl concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P less than 0.01). It is concluded that A1-receptors are located within the JGA, and that A1-receptor activation inhibits renin release. A high NaCl concentration at the macula densa appears to influence A1-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion.
Weihprecht
H
H
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Lorenz
J N
JN
Schnermann
J
J
Skøtt
O
O
Briggs
J P
JP
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008138:Loop of Henle / Q000187:drug effects / Q000201:enzymology; D010477:Perfusion; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D011983:Receptors, Purinergic; D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; D012965:Sodium Chloride; C051360:1,3-dipropyl-8-cyclopentylxanthine; D012083:Renin; D000241:Adenosine