Suppression of rat deoxycorticosterone-salt hypertension by kallikrein-kinin system.
Brown Norway kininogen-deficient rats had very low levels of plasma kininogens and lower levels of plasma prekallikrein, compared with those of normal rats of the same strain. Systolic blood pressure, determined by the tail-cuff method, of 5-week-old kininogen-deficient rats (106 +/- 0.4 mm Hg, n = 7) and the rate of systolic blood pressure increase with age were not different from those in normal rats. Weekly injections of deoxycorticosterone acetate (5 mg/kg s.c.) with 1% sodium chloride solution in drinking water after uninephrectomy at 7 weeks of age caused a gradual increase in the blood pressure of normal rats, reaching a plateau at 18 weeks of age, whereas that of deficient rats rose rapidly to 158 +/- 6 mm Hg 2 weeks after the start of treatment and continued to increase slightly, becoming significantly higher than normal rats at 8, 9, 10, 11, and 12 weeks of age (p less than 0.05 or 0.01). The levels of urinary prokallikrein and active kallikrein were slightly higher in deficient rats before deoxycorticosterone acetate-salt treatment but were not significantly increased after this treatment, whereas these levels in normal rats were increased 3.6- and 4.7-fold by this treatment. Urinary free kinin, collected from the ureter in untreated deficient rats, was below the detection limit. The plasma level of low molecular weight kininogen, the substrate of glandular kallikrein, was decreased in normal rats during the treatment. Continuous subcutaneous injection of aprotinin by an osmotic pump to normal rats induced significant increase in blood pressure. These results indicate that glandular kallikrein may play a suppressive role in deoxycorticosterone acetate-salt hypertension.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Katori
M
M
Hanazuka
M
M
Mizogami
S
S
Nakano
T
T
Nakao
Y
Y
Mikami
R
R
Uryu
H
H
Okamura
R
R
Mohsin
S S
SS
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006973:Hypertension / Q000517:prevention & control*; D016234:Kallikrein-Kinin System; D007704:Kininogens / Q000097:blood; D007705:Kinins / Q000652:urine; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D012965:Sodium Chloride / Q000652:urine
D007704:Kininogens; D007705:Kinins; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D007611:Aprotinin; D011188:Potassium