Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II.
The hemodynamic and endocrine effects of bradykinin and kininogens were investigated using a closed-circuit isolated rat kidney perfused with angiotensin II (ANG II). ANG II induced vasoconstriction, stimulation of urinary kallikrein release, and inhibition of renin secretion. Bradykinin markedly increased renal perfusate flow (RPF) and produced a slight but significant diuresis and natriuresis. The inhibitory effect of ANG II on renin secretion was delayed. Urinary kallikrein secretion was unchanged. The effect of bradykinin was suppressed by the competitive kinin antagonist [DArg,Hyp3,Thi5,8,DPhe7]bradykinin. Kallikrein-sensitive rat high-molecular-weight kininogen produced a progressive rise in renal perfusate flow. Exocrine function and renin and kallikrein secretions were unchanged. Immunoreactive kinins, identified as bradykinin by high-pressure liquid chromatography, were liberated into the perfusate. Perfusate immunoreactive high-molecular-weight kininogen decreased in parallel as a result of consumption. The kalikrein-resistant T-kininogen was not hydrolyzed to release a kinin, had no effect on renal function, and its concentration in the perfusate remained constant. These results suggest that kinin can be produced in the renal circulation from kallikrein-sensitive circulating kininogens and can antagonize the vasoconstrictor effect of ANG II and alter renal hemodynamics. They provide evidence that the kallikrein-kinin system can participate with the renin-angiotensin system in the control of renal blood flow.
Gardes
J
J
Pathologie Vasculaire et Endocrinologie Renale, Institut National de la Santé et de la Recherche Médicale U 36, Paris, France.
Baussant
T
T
Corvol
P
P
Ménard
J
J
Alhenc-Gelas
F
F
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D007704:Kininogens / Q000494:pharmacology*; D007705:Kinins / Q000037:antagonists & inhibitors; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction
D007704:Kininogens; D007705:Kinins; D000804:Angiotensin II; D001920:Bradykinin