Hypertension, Vol 24, 111-119, Copyright © 1994 by American Heart Association
M Majima, S Mizogami, Y Kuribayashi, M Katori and S Oh-ishi
Brown Norway Katholiek rats with 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 (132 +/- 2 mmHg, n = 7) was not different from that of
normal rats. Angiotensin II (Ang II) (20 micrograms/d SC) from 7 weeks of
age for 2 weeks with a micro-osmotic pump caused significant increases in
blood pressure (181 +/- 5 mm Hg, n = 7, 9 weeks old) in the deficient rats,
although the same treatment induced no blood pressure increase in the
normal rats. Also during this period, the deficient rats had significantly
higher heart rates, tended to excrete less urinary sodium, and showed
significantly higher sodium levels in serum, erythrocytes, and
cerebrospinal fluid compared with the normal rats. Ang II increased urinary
excretion of aldosterone in both deficient and normal rats (P < .05).
Spironolactone treatment (50 mg/kg per day) for 7 days in deficient rats
restored blood pressure and heart rate to normal levels and significantly
reduced sodium levels in erythrocytes and cerebrospinal fluid. Subcutaneous
infusion of bovine low-molecular-weight kininogen with an osmotic pump in
Ang II-treated deficient rats induced significant reductions in blood
pressure, heart rate, and erythrocyte sodium levels. By contrast,
subcutaneous infusion of the bradykinin antagonist Hoe 140 in Ang
II-treated normal rats induced a hypertensive response in parallel with
significant increases in heart rate and erythrocyte sodium level. These
results suggest that the lack of kinin generation observed in the
kininogen-deficient rats may cause the hypertensive response during the
administration of a nonpressor dose of Ang II mainly through sodium
retention probably caused by aldosterone release.
ARTICLES
Hypertension induced by a nonpressor dose of angiotensin II in kininogen-deficient rats
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
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