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(Hypertension. 1997;29:471.)
© 1997 American Heart Association, Inc.

State-of-the-Art-Lecture

Kallikrein-Kinin System and Blood Pressure Sensitivity to Salt

Paolo Madeddu; Maria Vittoria Varoni; Maria Piera Demontis; Julie Chao; Jo Anne Simson; Nicola Glorioso; Vittorio Anania

From the Clinica Medica (P.M., N.G.) and Farmacologia (M.V.V., M.P.D., V.A.), University of Sassari, Italy; National Institute of Biostructures and Biosystems (P.M.), Osilo, Italy; and Departments of Biochemistry and Molecular Biology (J.C.) and Anatomy and Cell Biology (J.A.S.), Medical University of South Carolina, Charleston.

Correspondence to Paolo Madeddu, MD, Clinica Medica, University of Sassari, Viale S. Pietro 8, 07100 Sassari, Italy. E-mail madeddu{at}mbox.vol.it

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 blood pressure was increased after 10 days of dietary sodium loading in the low-kallikrein group and remained unchanged in controls (153±1 versus 112±2 mm Hg, P<.01). In additional experiments, blood pressure sensitivity to salt was tested in low-kallikrein rats receiving a chronic infusion of rat glandular kallikrein (1.7 µg/day per 100 g body weight, IV) or vehicle. Systolic blood pressure of vehicle-treated 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 increased by kallikrein infusion (from 13.6±1.4 to 17.8±2.1 nanokatals per 24 hours; P<.01). Plasma immunoreactive kallikrein levels were 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 glomeruli 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 determined defect in urinary kallikrein excretion. Histological abnormalities are present at different levels in the nephron, and they may be functionally related to the altered cardiovascular and renal phenotype of this strain.

Key Words: sodium • kinins • blood pressure

Abbreviations: BW = body weight • HR = heart rate • kat = katal • MBP = mean blood pressure • PBS = phosphate-buffered saline • RUK = rat urinary kallikrein • SBP = systolic blood pressure • U_Cr = urinary creatinine • U_CrV = urinary creatinine excretion • U_Kall = kallikrein activity in urine • U_KallV = urinary kallikrein excretion • U_Na = sodium concentration in urine • U_NaV = urinary sodium excretion • UV = urinary volume

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