This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saitoh, S. Articles by Carretero, O. A. Search for Related Content PubMed PubMed Citation Articles by Saitoh, S. Articles by Carretero, O. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB SODIUM

(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

This article has been cited by other articles:

				S.-H. Sivritas, D. W. Ploth, and W. R. Fitzgibbon Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet Am J Physiol Renal Physiol, September 1, 2008; 295(3): F811 - F817. [Abstract] [Full Text] [PDF]

				H. Peng, O. A. Carretero, M. E. Alfie, J. A. Masura, and N.-E. Rhaleb Effects of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Type 1 Receptor Antagonist in Deoxycorticosterone Acetate-Salt Hypertensive Mice Lacking Ren-2 Gene Hypertension, March 1, 2001; 37(3): 974 - 980. [Abstract] [Full Text] [PDF]

				J. Tornel, M. I. Madrid, M. Garcia-Salom, K. J. Wirth, and F. J. Fenoy Role of Kinins in the Control of Renal Papillary Blood Flow, Pressure Natriuresis, and Arterial Pressure Circ. Res., March 17, 2000; 86(5): 589 - 595. [Abstract] [Full Text] [PDF]

				M. E. Alfie, S. Alim, D. Mehta, E. G. Shesely, and O. A. Carretero An Enhanced Effect of Arginine Vasopressin in Bradykinin B2 Receptor Null Mutant Mice Hypertension, June 1, 1999; 33(6): 1436 - 1440. [Abstract] [Full Text] [PDF]

				H. M. Siragy, A. A. Jaffa, and H. S. Margolius Bradykinin B2 Receptor Modulates Renal Prostaglandin E2 and Nitric Oxide Hypertension, March 1, 1997; 29(3): 757 - 762. [Abstract] [Full Text]

				M. E. Alfie, D. H. Sigmon, S. I. Pomposiello, and O. A. Carretero Effect of High Salt Intake in Mutant Mice Lacking Bradykinin-B2 Receptors Hypertension, January 1, 1997; 29(1): 483 - 487. [Abstract] [Full Text] [PDF]