Differential regulation of kallikrein, kininogen and kallikrein
-binding protein in arterial hypertensive rats.
Chao, Caroline, Paolo Madeddu, Cindy Wang, Yumei Liang, Lee Chao, and
Julie Chao.
Department of Biochemistry and Molecular Biology, Medical
University of South Carolina, Charleston, South Carolina 29425, USA,
Clinica Medica, University of Sassari, Sassari, Italy
APStracts 3:0021F, 1996.
This study was designed to determine if the kallikrein-kinin system
exerts a protective action in hypertension induced by chronic
inhibition of nitric oxide synthase. Nw-nitro-L-arginine methyl ester
(L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats,
while controls received regular tap water. Hepatic kininogen mRNA
levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3
and 4 weeks, respectively, as compared to control rats, while
kallikrein-binding protein mRNA levels were 82% and 45% of the values
found in control rats at 3 and 4 weeks, respectively. There was no
significant change in hepatic a1-antitrypsin mRNA levels under the
same conditions. At 3 and 4 weeks post L-NAME treatment, renal
kallikrein mRNA levels were 2.5- and 3.4-fold higher than in
controls, while renal b-actin mRNA levels were similar between
groups. Changes in the transcript levels of renal kallikrein,
kininogen and kallikrein-binding protein were consistent with their
protein levels. Immunoreactive total kininogen and low Mr kininogen
levels in sera and tissue kallikrein levels in kidney were
significantly higher in the L-NAME treated-group, while kallikrein
-binding protein levels in the circulation were lower compared with
controls. Systolic blood pressure was increased by 58 4 mmHg after 4
weeks of L-NAME treatment. This effect was enhanced in rats given L
-NAME in combination with Hoe 140, a bradykinin B2-receptor
antagonist, at the dose of 100 g/day intraperitoneally (79 5 vs 58 4
mmHg, P<0.05). This difference was confirmed by direct
measurement of mean blood pressure. An intra-arterial bolus injection
of 200 ng bradykinin significantly decreased mean blood pressure of
L-NAME-treated rats, and this effect was blunted in the group treated
with the bradykinin antagonist (-29 3 vs -9 2 mmHg, P<0.01).
These results suggest that enhanced kallikrein and kininogen
synthesis may have a protective role against the cardiovascular
effects induced by chronic inhibition of nitric oxide synthesis.
Received 14 August 1995; accepted in final form 2 January 1996.
APS Manuscript Number F271-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96