Hypertension induced by a nonpressor dose of angiotensin II in kininogen-deficient rats.
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.
Majima
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Mizogami
S
S
Kuribayashi
Y
Y
Katori
M
M
Oh-ishi
S
S
D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007704:Kininogens / Q000172:deficiency*; D007705:Kinins / Q000652:urine; D008297:Male; D008970:Molecular Weight; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
D007704:Kininogens; D007705:Kinins; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D012964:Sodium