Interactions between bradykinin and ANP in rat kidney in vitro: inhibition of natriuresis and modulation of medullary cyclic GMP.
In anesthetized rats, the renal excretory actions of atrial natriuretic peptide (ANP) are inhibited by intravenous or intraperitoneal injections of bradykinin. To elucidate the mechanisms underlying this inhibition, we evaluated bradykinin effects on: i- ANP-induced natriuresis and diuresis in isolated perfused rat kidneys, and ii- ANP-induced cGMP production in rat renal medulla in vitro. In perfused kidneys, 1 microgram bradykinin completely inhibited the diuretic and natriuretic responses elicited by 0.5 microgram ANP, without changes in perfusion pressure. The inhibitory effects of bradykinin were abolished by HOE-140, a kinin-B2 receptor antagonist. Bradykinin alone had no effect on urinary excretion or perfusion pressure. Incubation with ANP (0.1 nM to 1 microM) increased renal medullary cGMP content up to 30-fold, in a concentration-dependent fashion. Medullary cGMP was moderately increased by the nitric oxide donor, sodium nitroprusside (1 microM), but it was unchanged by bradykinin (0.1 nM-0.1 microM). Despite this, ANP-induced cGMP production was significantly enhanced by co-incubation with low concentrations of bradykinin (up to 0.1 nM). In contrast, ANP-induced cGMP accumulation was unchanged by concentrations of 1 nM bradykinin or higher. In the presence of 100 nM HOE-140, bradykinin (0.1-1 nM) did not affect ANP-induced cGMP production. These results demonstrate that bradykinin counteracts ANP-stimulated sodium and water excretion, by acting directly on the kidney. The interaction between both peptides is complex; our data suggest that renal medullary ANP receptors are subjected to an on/off modulation by fluctuating bradykinin concentrations.
Boric
M P
MP
Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. mboric@genes.bio.puc.cl
Bravo
J A
JA
Corbalan
M
M
Vergara
C
C
Roblero
J S
JS
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D001920:Bradykinin