C. Damasemichel et al., RELATIONSHIPS BETWEEN KALLIKREIN SECRETION, KALLIKREIN EXCRETION AND BETA-ADRENOCEPTORS IN KIDNEY CORTICAL SLICES FROM NEUROGENIC HYPERTENSIVE DOGS, British Journal of Pharmacology, 116(1), 1995, pp. 1704-1710
1 Sinoaortic denervation (SAD) in dogs is characterized by an increase
in blood pressure and heart rate as well as the development of renal
morphological lesions similar to those observed in essential hypertens
ion in human subjects. To assess the effect of SAD on the secretion of
kallikrein kinin systems (KKS), we studied the in vitro secretion of
kallikrein by renal cortical slices of normal and neurogenic hypertens
ive dogs (1 and 18 months after SAD). The method using renal cortical
slices allowed the study of secretion of kallikrein independently of r
enal perfusion pressure. The number of renal beta-adrenoceptors was me
asured by [I-125]-cyanopindolol binding. 2 SAD was associated with a m
arked increase in urinary kallikrein excretion at one month and a sign
ificant decrease at 18 months when compared with controls. Both change
s were statistically significant (P < 0.05). Concurrently, a progressi
ve increase in in vitro kallikrein secretion was observed (+ 80 +/- 10
% and + 179 +/- 48%, 1 and 18 months after SAD, respectively). Moreove
r, the cortical slices obtained from sinoaortic denervated dogs contai
ned more kallikrein than the control cortical slices (+ 32 +/- 16% and
+ 55 +/- 7%, 1 and 18 months after SAD, respectively). 3 Renal beta-a
drenoceptor number significantly (P < 0.05) decreased 18 months after
SAD from 18 +/- 2 to 8 +/- 3 fmol mg(-1) protein without any change in
affinity constant. 4 Although there was no test of association, becau
se the number of renal beta-adrenoceptors decreased whereas kallikrein
secretion increased, the present data could suggest a beta-adrenocept
or-mediated inhibition of kallikrein secretion. These results show tha
t although the urinary kallikrein is decreased, the tissue secretory c
apacities are enhanced. This could suggest a renal compensatory mechan
ism possibly involved in tissue protection in dogs after SAD, although
such a mechanism is not sufficient to reverse hypertension.