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(Hypertension. 1995;25:1008-1013.)
© 1995 American Heart Association, Inc.

Articles

Effect of Inhibiting Renal Kallikrein on Prostaglandin E₂, Water, and Sodium Excretion

Shigeyuki Saitoh; A. Guillermo Scicli; Edward Peterson; Oscar A. Carretero

From the Hypertension and Vascular Research Division, Department of Medicine and Heart and Vascular Institute, and the Division of Biostatistics and Research Epidemiology (E.P.), Henry Ford Hospital, Detroit, Mich.

Correspondence to Oscar A. Carretero, MD, Hypertension and Vascular Research Division, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI 48202-2689.

Abstract To test the hypothesis that renal kinins act as natriuretic and diuretic hormones, we examined the effect of inhibiting glandular kallikrein on renal function in normotensive unanesthetized rats during normal sodium intake. To inhibit kallikrein at both the luminal and basolateral sides of the distal nephron, we used Fab fragments of monoclonal antibodies to rat urinary kallikrein (Fab-kallikrein). Fab fragments have advantages over intact IgG: they are filtered through the glomerulus and reach the lumen of the distal nephron, where kallikrein is localized and urinary kinins are released. Furthermore, the Fab fragment–antigen complex does not activate the complement system, avoiding the side effects associated with intact antibodies. Fab-kallikrein effectively blocked generation of kinins in the nephron lumen, decreasing urinary kininogenase activity (kallikrein) by 74% to 85% and kinin excretion by 76% to 79%. Fab-kallikrein induced a 30% decrease in urine volume and a 20% to 40% decrease in urinary sodium excretion but did not alter blood pressure, glomerular filtration rate, or renal blood flow. Although urinary prostaglandin E₂ excretion also tended to decrease, this change was slower and of lesser magnitude than those of kinin and kininogenase excretion and did not attain statistical significance after Bonferroni's correction. In controls injected with either vehicle or Fab fragments of monoclonal antibodies to ricin (a vegetable protein not present in mammals), none of these parameters decreased significantly. We conclude that renal kinins participate in the short-term regulation of water and sodium excretion in normotensive unanesthetized rats, acting as diuretic and natriuretic hormones. Kinins acting on the distal nephron, either directly or via release of nitric oxide and/or prostaglandins, are likely responsible.

Key Words: kallikrein • kallikrein-kinin system • prostaglandins • sodium • body water • kidney function

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