Role of the kallikrein-kinin system in the maturation of cardiovascular phenotype

Recent studies indicate that during early phases of life the kallikrein-kin in system (KKS) plays a role in kidney development, In the rat kidney, the spatial and temporal pattern of expression of the genes encoding for kallik rein or bradykinin (BK) B-2-receptors parallels postnatal nephrogenesis and blood now redistribution from the inner to the outer renal cortex. Animal models with genetic dysfunction of the renal KKS show alterations in the fu nctional maturation of the kidney, and ultimately develop salt-sensitive hy pertension. Kininogen-deficient Brown Norway Katholiek rats have undetectab le urinary kinin levels and show an exaggerated blood pressure sensitivity to chronic excess of salt or mineralocorticoids. Another rat model with gen etic reduction in urinary kallikrein excretion is characterized by an alter ed pressure-natriuresis relationship, with this defect being corrected by i nfusion of purified rat tissue kallikrein. Knockout mice lacking the BK B-2 -receptor gene show elevated blood pressure and heart rate under basal cond itions and enhanced blood pressure sensitivity to salt. In rats, prenatal b lockade of the BK B-2-receptor by icatibant leads to a cardiovascular pheno type similar to that of animals with genetic defects of the KKS. Delayed re nal maturation is observed when high salt intake is associated with icatiba nt. Collectively, these findings indicate a relevant role of the KKS in the physiologic maturation of renal and cardiovascular phenotypes. Genetic or environmental factors, able to potentiate the activity of the renal KKS, co uld protect against the development of arterial hypertension. (C) 1999 Amer ican Journal of Hypertension, Ltd.