ROLE OF THE RENAL KALLIKREIN-KININ SYSTEM IN THE DEVELOPMENT OF HYPERTENSION

Role of renal kallikrein-kinin system has been studied using mutant Br own-Norway Katholiek (BN-Ka) rats, in which both high- and low- molecu lar weight kininogens were almost absent in plasma and kinin in urine was mainly not detectable. Mutant BN-Ka rats were very sensitive to in creased salt intake, resulting in raised systemic blood pressure that is linked to reduced urinary excretion of sodium, when compared with n ormal BN-Kitasato (BN-Ki) rats. Consequently, sodium accumulated in er ythrocytes and cerebrospinal fluid in mutant BN-Ka rats. Subcutaneous infusion of angiotensin II (20 mg/day/rat) also enhanced the concentra tion of sodium in erythrocytes and in cerebrospinal fluid and increase d 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 presser responses of the arterioles to norepinephrine and angiotensin II (i.a.) by 30- and 10-fold, respectively. Infusion of ebelactone B, (a selective inhibit or of carboxypeptidase Y-like exopeptidase, a kininase in rat urine), to normal BN-Ki rats during induction of hypertension with DOCA and sa lt, resulted in the reduction of the raised blood pressure, indicating that a site of action of kinins was at the luminal membrane of the re nal 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 o f hypertension as a result of the sodium accumulation in the body.