Renal effects of Fab fragments of kinin antibodies on deoxycorticosterone acetate-salt-treated rats.
The role of the renal kallikrein-kinin system in the regulation of renal function is not completely understood. Intrarenal kinins can influence renal function by acting as paracrine hormones at basolateral, luminal, or both sites in the distal nephron. To examine the role of intrarenal kinins in deoxycorticosterone acetate-salt-treated rats, which have high renal kallikrein, Fab fragments of antibradykinin antibody or DArg[Hyp3Thi5,8DPhe7]bradykinin, a kinin antagonist, were used to block kinins. At the dose used, the antibody (25 mg) and kinin antagonist (10 micrograms/min/rat) inhibited the hypotensive effect of intra-arterially injected bradykinin (100 ng) by 70% and 52%, respectively. The antibody appeared in the urine within 30 minutes after administration. Urinary volume was lowered from 9.4 +/- 0.2 to 6.7 +/- 0.4 microliters/min/g kidney wt (p less than 0.001, paired t test) by the antibody and from 8.5 +/- 0.3 to 6.8 +/- 0.4 microliters/min/g kidney wt (p less than 0.004, paired t test) by the kinin antagonist. The antibody lowered urine sodium excretion from 1.11 +/- 0.04 to 0.88 +/- 0.06 mueq/min/g kidney wt (p less than 0.001, paired t test), whereas the kinin antagonist had no significant effect. Neither altered blood pressure, renal blood flow, or glomerular filtration rate. These data suggest that in deoxycorticosterone acetate-salt-treated rats, excretion of water and sodium is regulated in part by kinins. The antidiuretic effect of the antibody and kinin antagonist might be due to blockade of kinins in the vascular-interstitial space of the kidney, since the kinin antagonist is likely hydrolyzed in the proximal tubule and does not reach the lumen of the distal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)
Tomiyama
H
H
Henry Ford Hospital, Hypertension Research Division, Detroit, Michigan 48202.
Scicli
A G
AG
Scicli
G M
GM
Carretero
O A
OA
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001920:Bradykinin / Q000276:immunology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004231:Diuresis; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D007705:Kinins / Q000276:immunology*; D008297:Male; D009318:Natriuresis; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology*
D000906:Antibodies; D007140:Immunoglobulin Fab Fragments; D007705:Kinins; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D001920:Bradykinin