Postnatal maturation of the kallikrein-kinin system in the rat kidney: From enzyme activity to receptor gene expression

During the course of aging, the balance between intrarenal hormones is disturbed, These age-related changes are well documented for the vasoconstrictor renin-angiotensin system, but comparable information on the renal kallikrein-kinin system is not yet available, The status of the kallikrein-kinin system was assessed by (1) kallikrein activity, measured by RIA; (2) maximum binding site density (Bmax) and affinity (K(d)) of nonapeptide bradykinin (BK)-2 receptor, estimated by binding assays; (3) expression of BK2-receptor mRNA, detected by reverse transcription-polymerase chain reaction (RT-PCR) using specific BK2-oligonucleotide primers. These parameters were determinated on renal glomeruli of 3-, 5-, 8-, 12- and 38-wk-old normotensive rats. Kallikrein activity increased from 3.2 to 7.7 ng BK/min per mg protein. The density of BK2 binding sites also rose from 12 to 40 femtomoles/mg protein with no difference in affinity. There was no change in specificity, which remained that expected of a BK2 receptor. The increase in the density of BK2 binding sites was associated with an augmented mRNA expression, whereas p-actin mRNA used as a control remained unchanged. The ratio of BK2 mRNA to β-actin mRNA indicated maximum steady expression after 8 wk of age. The data provide evidence that the renal kallikrein-kinin system develops postnatally.