RELATIONSHIPS BETWEEN KALLIKREIN SECRETION, KALLIKREIN EXCRETION AND BETA-ADRENOCEPTORS IN KIDNEY CORTICAL SLICES FROM NEUROGENIC HYPERTENSIVE DOGS

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.