Development biology of the renal kallikrein-kinin system.

Kinins are endothelium-dependent vasodilators and natriuretic paracrine peptides that participate in the regulation of blood pressure, renal hemodynamics and sodium excretion. Several lines of evidence suggest an important role for intrarenal kinins and their receptors in kidney growth and development. (1) The developing rat kidney expresses all the components of the tissue kallikrein-kinin system: tissue kallikrein, low molecular weight (LMW) kininogen, kininase II and kinin receptors. Also, the developing liver expresses high molecular weight and LMW kininogens. Thus, a complete kinin-generating system exists in the developing kidney. (2) Gene transcription, mRNA and protein abundance, and enzymatic activity of renal kallikrein are all markedly up-regulated during postnatal kidney growth, and a positive correlation exists between renal kallikrein synthesis and the maturational rise in renal blood flow. (3) Rat glomerular mesangial cells in culture express the kinin receptors and proliferate in response to bradykinin, suggesting that endogenous kinins and their receptors modulate glomerular growth. (4) The newborn period is characterized by an activation of kinin receptor gene expression, and chronic pharmacological blockade of kinin receptors suppresses DNA synthesis in the developing but not adult kidney. Collectively, these data provide the basis for the hypothesis that endogenous kinins and the kinin receptors play an important role in the developmental biology of the metanephric kidney.