AJP - Renal Physiology, Vol 273, Issue 5 783-F789, Copyright © 1997 by American Physiological Society
Effect of cyclosporin A on the expression of tissue kallikrein, kininogen, and bradykinin receptor in rat
C. Wang, P. Ford, C. Chao, L. Chao and J. Chao
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425-2211, USA.
The tissue kallikrein-kinin system is involved in vasodilation and blood
pressure regulation. In the present study, we investigated the effects of
chronic cyclosporin A (CsA) administration on blood pressure and the
expression of tissue kallikrein, kininogen, and bradykinin receptor in
normotensive Wistar rats. Chronic administration of CsA significantly
increased systolic blood pressure compared with control rats (n = 6, P <
0.01), although body weight was significantly lower than control rats (n =
6, P < 0.01). The development of hypertension was accompanied by the
altered expression of kallikrein-kinin system components. Immunoreactive
renal kallikrein and urinary excretion of tissue kallikrein levels were
increased by chronic administration of CsA (n = 5 or 6, P < 0.05).
Levels of N-tosyl-L-phenylalanine chloromethyl ketone-trypsin and
kallikrein-releasable kininogens in sera increased in response to chronic
CsA treatment (n = 5 or 6, P < 0.05). Chronic CsA treatment
significantly increased renal kallikrein, bradykinin B2 receptor, and
hepatic kininogen mRNA levels. The increased levels of tissue
kallikrein-kinin system components were accompanied by significant
increases in 24-h urine excretion and water intake after chronic CsA
treatment (n = 5, P < 0.05). These results suggest that enhanced
activity of the tissue kallikrein-kinin system may compensate for the
CsA-induced vasoconstriction and hypertension.
