KALLIKREIN-KININ SYSTEM AND BLOOD-PRESSURE SENSITIVITY TO SALT

We evaluated the blood pressure response to chronic salt loading in a rat strain inbred for low urinary kallikrein excretion. Low-kallikrein rats showed greater systolic blood pressure values (130 +/- 1 versus 114 +/- 2 mm Hg in controls; P < .05) at 9 weeks of age. Systolic bloo d pressure was increased after 10 days of dietary sodium loading in th e low-kallikrein group and remained unchanged in controls (153 +/- 1 v ersus 112 +/- 2 mm Hg, P < .01). In additional experiments, blood pres sure sensitivity to salt was tested in low-kallikrein rats receiving a chronic infusion of rat glandular kallikrein (1.7 mu g/day per 100 g body weight, IV) or vehicle. Systolic blood pressure of vehicle-treate d rats was increased by salt loading (from 138 +/- 1 to 158 +/- 2, 153 +/- 1, and 145 +/- 2 mm Hg at 5, 10, and 15 days, respectively; P < . 01), while it remained unchanged in the kallikrein-treated group (from 136 +/- 2 to 146 +/- 5, 140 +/- 2, and 134 +/- 4 mm Hg at 5, 10, and 15 days, respectively; P = NS). Urinary kallikrein excretion was incre ased by kallikrein infusion (from 13.6 +/- 1.4 to 17.8 +/- 2.1 nanokat als per 24 hours; P < .01). Plasma immunoreactive kallikrein levels we re higher in the kallikrein-treated group (66.4 +/- 4.4 versus 57.7 +/ - 1.4 ng/mL in vehicle-treated rats; P < .05). On normal sodium diet, the ratio of kidney weight to body weight was lower in low-kallikrein rats (329 +/- 5 versus 370 +/- 8 mg/100 g body weight in controls; P < .01). This difference was associated with a decreased number of glome ruli per unit square area and increased width of Bowman's space. These results indicate that kallikrein replacement prevents the exaggerated blood pressure increase observed in rats with a genetically determine d defect in urinary kallikrein excretion. Histological abnormalities a re present at different levels in the nephron, and they may be functio nally related to the altered cardiovascular and renal phenotype of thi s strain.