High sensitivity to salt in kininogen-deficient brown Norway Katholiek rats.
Brown Norway Katholiek rats, which have very low levels of plasma kininogens, excreted a much smaller amount of kinin in the urine than normal rats of the same strain. The systolic blood pressure of 7-week-old kininogen-deficient rats fed low (0.3%) NaCl diets (131 +/- 4 mm Hg, n = 12) was not different from that in normal rats. Two percent NaCl diets given from 7 weeks of age for 4 weeks caused rapid increases in blood pressure (167 +/- 4 mm Hg, n = 12, 9 weeks old) in deficient rats, although the same diets induced no blood pressure increase in normal rats. Urinary excretion of active kallikrein and prokallikrein remained constant in both rat groups throughout NaCl loading. During this period, the deficient rats secreted less urine (9 weeks old, P < .05) and less urinary sodium (11 weeks old, P < .05). Serum levels of sodium in deficient rats were higher (P < .05) than in normal rats at 9 weeks of age. Intracellular concentrations of sodium in the erythrocytes of deficient rats were higher (P < .05) than in normal rats throughout NaCl loading. Subcutaneous infusion of bovine low molecular weight kininogen with an osmotic pump in NaCl-loaded deficient rats induced a reduction (P < .01) in blood pressure and increases (P < .05) in urine volume and urinary sodium and kinin levels. By contrast, subcutaneous infusion of the bradykinin antagonist Hoe 140 or of aprotinin in NaCl-loaded normal rats induced a hypertensive response. This antagonist treatment reduced urine volume and urinary sodium. These results indicate that the lack of kinin generation observed in the kininogen-deficient rats was related through sodium retention to the hypertensive response to NaCl loading.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Yoshida
O
O
Mihara
H
H
Muto
T
T
Mizogami
S
S
Kuribayashi
Y
Y
Katori
M
M
Oh-ishi
S
S
D000375:Aging / Q000502:physiology; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003404:Creatinine / Q000097:blood / Q000652:urine; D004912:Erythrocytes / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007704:Kininogens / Q000172:deficiency* / Q000494:pharmacology*; D007705:Kinins / Q000652:urine; D011188:Potassium / Q000097:blood / Q000652:urine; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D012016:Reference Values; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000652:urine; D012982:Sodium, Dietary / Q000494:pharmacology*
D007704:Kininogens; D007705:Kinins; D012982:Sodium, Dietary; C065679:icatibant; D007611:Aprotinin; D012964:Sodium; D003404:Creatinine; D012083:Renin; D011188:Potassium; D001920:Bradykinin