Role of the renal kallikrein-kinin system in the development of hypertension.

Role of renal kallikrein-kinin system has been studied using mutant Brown-Norway Katholiek (BN-Ka) rats, in which both high- and low-molecular weight kininogens were almost absent in plasma and kinin in urine was mainly not detectable. Mutant BN-Ka rats were very sensitive to increased salt intake, resulting in raised systemic blood pressure that is linked to reduced urinary excretion of sodium, when compared with normal BN-Kitasato (BN-Ki) rats. Consequently, sodium accumulated in erythrocytes and cerebrospinal fluid in mutant BN-Ka rats. Subcutaneous infusion of angiotensin II (20 mg/day/rat) also enhanced the concentration of sodium in erythrocytes and in cerebrospinal fluid and increased the systemic pressure by releasing aldosterone. A 4-day infusion of 0.3 M sodium solution (6 ml/kg/h) to the abdominal aorta of conscious and un-restrained mutant BN-Ka rats increased the pressor responses of the arterioles to norepinephrine and angiotensin II (i.a.) by 30- and 10-fold, respectively. Infusion of ebelactone B, (a selective inhibitor of carboxypeptidase Y-like exopeptidase, a kininase in rat urine), to normal BN-Ki rats during induction of hypertension with DOCA and salt, resulted in the reduction of the raised blood pressure, indicating that a site of action of kinins was at the luminal membrane of the renal tubule cells. Our results support the view that the role of renal kallikrein-kinin system is to excrete 'excess sodium' and a reduction in the generation of renal kinins may be a factor in the development of hypertension as a result of the sodium accumulation in the body.