Effects of a kinin antagonist on renal function in rats.
We contrasted the effects of D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg-TFA (kinin receptor antagonist), of aprotinin (kallikrein inhibitor), and of combined treatment with captopril (kininase II inhibitor) and phosphoramidon (neutral endopeptidase 24.11 inhibitor) on renal function of rats with and without 14-day deoxycorticosterone pretreatment (DOC, 25 mg.kg-1.wk-1 sc). Neither the kinin antagonist nor aprotinin affected renal function in rats with and without DOC pretreatment. Combined treatment with captopril and phosphoramidon caused in rats with and without DOC pretreatment augmentation (P less than 0.05) of kinin excretion (50-64%), glomerular filtration rate (12-11%), and sodium excretion (46-48%). In DOC-pretreated rats undergoing infusion of captopril and phosphoramidon, the superimposed administration of either the kinin antagonist or aprotinin caused the lowering of renal plasma flow, glomerular filtration rate, and sodium excretion. These effects of the kinin antagonist and aprotinin in rats infused with kininase inhibitors may be the consequence of blockade, respectively, of the renal actions and synthesis of kinins that, when in excess, elicit renal vasodilation and increase glomerular filtration rate and sodium excretion. Collectively, these observations suggest regulatory influence of kinins during conditions featuring increased renal kinin levels.
Department of Pharmacology, University of Tennessee, Memphis 38163.
M
M
Nakagawa
J M
JM
Stewart
R J
RJ
Vavrek
A
A
Nasjletti
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007705:Kinins / Q000037:antagonists & inhibitors* / Q000652:urine; D009318:Natriuresis / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D006020:Glycopeptides; D007705:Kinins; D003900:Desoxycorticosterone; D007611:Aprotinin; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; C008890:phosphoramidon