Role of the kallikrein-kinin system in the maturation of cardiovascular phenotype.
Recent studies indicate that during early phases of life the kallikrein-kinin system (KKS) plays a role in kidney development. In the rat kidney, the spatial and temporal pattern of expression of the genes encoding for kallikrein or bradykinin (BK) B2-receptors parallels postnatal nephrogenesis and blood flow redistribution from the inner to the outer renal cortex. Animal models with genetic dysfunction of the renal KKS show alterations in the functional maturation of the kidney, and ultimately develop salt-sensitive hypertension. Kininogen-deficient Brown Norway Katholiek rats have undetectable urinary kinin levels and show an exaggerated blood pressure sensitivity to chronic excess of salt or mineralocorticoids. Another rat model with genetic reduction in urinary kallikrein excretion is characterized by an altered pressure-natriuresis relationship, with this defect being corrected by infusion of purified rat tissue kallikrein. Knockout mice lacking the BK B2-receptor gene show elevated blood pressure and heart rate under basal conditions and enhanced blood pressure sensitivity to salt. In rats, prenatal blockade of the BK B2-receptor by icatibant leads to a cardiovascular phenotype similar to that of animals with genetic defects of the KKS. Delayed renal maturation is observed when high salt intake is associated with icatibant. 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, could protect against the development of arterial hypertension.
Emanueli
C
C
National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
Madeddu
P
P
D000818:Animals; D001794:Blood Pressure; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007705:Kinins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D051381:Rats; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
D007705:Kinins; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D017673:Sodium Chloride, Dietary; D007610:Kallikreins