This Article Full Text Full Text (PDF) 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 Maly, J. Articles by El-Dahr, S. S. Search for Related Content PubMed PubMed Citation Articles by Maly, J. Articles by El-Dahr, S. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections Other hypertension

(Hypertension. 2001;37:967.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Angiotensin II–Induced Hypertension in Bradykinin B₂ Receptor Knockout Mice

Presented in part in abstract form at the Experimental Biology 2000 Meeting, April 10–13, 2000, San Diego, Calif.

Ludk ervenka; Jan Mal; Ludmila Karasová; Marcela imová; tefan Vítko; Soa Hellerová; Jií Heller; Samir S. El-Dahr

From the Department of Experimental Medicine (L.C., J.M., L.K., S.H., J.H.) and the Transplant Center (M.S., S.V.), Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Pediatrics (S.S.E.-D.), Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, La; and Department of Physiology, 2nd Medical Faculty Charles University, Prague, Czech Republic.

Correspondence to Ludk ervenka, MD, Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, 1958/9 Vídeská, 140 00 Prague 4, Czech Republic. E-mail luce{at}medicon.cz

The present study was performed to examine the role of endogenous bradykinin (BK) in the development of angiotensin II (Ang II)–induced hypertension in mice. BK B₂ receptor knockout (B₂R^-/-) and wild-type (B₂R^+/+) mice (22 to 26 g) were infused with either saline (SAL) or Ang II (40 ng/min) via an osmotic minipump implanted intraperitoneally. On day 12 after implantation, there was no difference in systolic blood pressure (SBP, tail-cuff plethysmography) between SAL/B₂R^+/+ and SAL/B₂R^-/- mice (128±5 versus 133±6 mm Hg, n=24/group). In contrast, SBP was higher on day 12 of infusion in Ang II/B₂R^-/- than in Ang II/B₂R^+/+ mice (173±6 versus 156±5 mm Hg; P<0.05, n=27 and 28). Mean arterial pressure (MAP) was also higher in anesthetized Ang II/B₂R^-/- mice than in Ang II/B₂R^+/+ mice (139±3 versus 124±3 mm Hg; P<0.05, n=16 and 14). Unlike Ang II, long-term norepinephrine (NE) infusion via an osmotic minipump (45 ng/min) caused equivalent increases in SBP in B₂R^+/+ and B₂R^-/- mice measured on day 12 after implantation (151±4 versus 149±5 mm Hg, n=9 and 8). MAP also did not differ on day 13 after implantation between NE/B₂R^+/+ and NE/B₂R^-/- mice (120±6 versus 122±4 mm Hg, n=9 and 8). There were no differences in glomerular filtration rate and urinary sodium excretion among the groups. However, renal plasma flow (RPF) was lower in Ang II/B₂R^-/- mice than in Ang II/B₂R^+/+ mice (2.34±0.06 versus 4.33±0.19 mL · min^-1 · g^-1; P<0.05). Acute inhibition of NO synthase (NOS) with nitro-L-arginine-methyl ester (0.5 µg · g^-1 · min^-1) in SAL/B₂^+/+ and SAL/B₂^-/- mice caused equal increases in MAP (142±1 versus 145±1 mm Hg) and decreases in RPF (2.06±0.06 versus 2.12±0.15 mL · min^-1 · g^-1). However, short-term NOS inhibition caused a greater increase in MAP of Ang II/B₂R^+/+ mice than of Ang II/B₂R^-/- mice, such that MAP after NOS inhibition in Ang II/B₂R^+/+ approached that of Ang II/B₂R^-/- mice (156±2 versus 159±2 mm Hg). These changes were associated with a decrease in RPF in Ang II/B₂R^+/+ mice to values similar to those of Ang II/B₂R^-/- mice before NOS inhibition (2.12±0.09 versus 2.34±0.06 mL · min^-1 · g^-1). These results demonstrate that the kallikrein-kinin system selectively buffers the vasoconstrictor activity of Ang II. Furthermore, the enhanced susceptibility of B₂R^-/- mice to Ang II–induced hypertension and renal vasoconstriction is likely due to an impaired ability to release NO by endogenous kinins.

Key Words: kallikrein-kinin system • angiotensin II • nitric oxide • blood pressure • norepinephrine • blood flow

This article has been cited by other articles:

				D. Zhao, D. M. Seth, and L. G. Navar Enhanced Distal Nephron Sodium Reabsorption in Chronic Angiotensin II-Infused Mice Hypertension, July 1, 2009; 54(1): 120 - 126. [Abstract] [Full Text] [PDF]

				R. A. Gonzalez-Villalobos, R. Satou, D. M. Seth, L. C. Semprun-Prieto, A. Katsurada, H. Kobori, and L. G. Navar Angiotensin-Converting Enzyme-Derived Angiotensin II Formation During Angiotensin II-Induced Hypertension Hypertension, February 1, 2009; 53(2): 351 - 355. [Abstract] [Full Text] [PDF]

				C. Hu, A. Dandapat, L. Sun, M. R. Marwali, N. Inoue, F. Sugawara, K. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, et al. Modulation of Angiotensin II-Mediated Hypertension and Cardiac Remodeling by Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Deletion Hypertension, September 1, 2008; 52(3): 556 - 562. [Abstract] [Full Text] [PDF]

				G. J Dietze and E. J Henriksen Review: Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis Journal of Renin-Angiotensin-Aldosterone System, June 1, 2008; 9(2): 75 - 88. [Abstract] [PDF]

				B. Shen, L. M. Harrison-Bernard, A. J. Fuller, V. Vanderpool, Z. Saifudeen, and S. S. El-Dahr The Bradykinin B2 Receptor Gene Is a Target of Angiotensin II Type 1 Receptor Signaling J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1140 - 1149. [Abstract] [Full Text] [PDF]

				N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]

				L. M. F. Leeb-Lundberg, F. Marceau, W. Muller-Esterl, D. J. Pettibone, and B. L. Zuraw International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences Pharmacol. Rev., March 1, 2005; 57(1): 27 - 77. [Abstract] [Full Text] [PDF]

				L. M. Harrison-Bernard, S. Dipp, and S. S. El-Dahr Renal and blood pressure phenotype in 18-mo-old bradykinin B2R(-/-)CRD mice Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R782 - R790. [Abstract] [Full Text] [PDF]

				A. H. Schmaier The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2003; 285(1): R1 - R13. [Abstract] [Full Text] [PDF]

				J. P. Schanstra, J. Duchene, F. Praddaude, P. Bruneval, I. Tack, J. Chevalier, J.-P. Girolami, and J.-L. Bascands Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting Enzyme Systems: Decreased renal NO excretion and reduced glomerular tuft area in mice lacking the bradykinin B2 receptor Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1904 - H1908. [Abstract] [Full Text] [PDF]

				H. D. Xiao, S. Fuchs, J. M. Cole, K. M. Disher, R. L. Sutliff, and K. E. Bernstein Regulation of Cardiovascular Signaling by Kinins and Products of Similar Converting-Enzyme Systems: Role of bradykinin in angiotensin-converting enzyme knockout mice Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H1969 - H1977. [Abstract] [Full Text] [PDF]

				N. Kawada, E. Imai, A. Karber, W. J. Welch, and C. S. Wilcox A Mouse Model of Angiotensin II Slow Pressor Response: Role of Oxidative Stress J. Am. Soc. Nephrol., December 1, 2002; 13(12): 2860 - 2868. [Abstract] [Full Text] [PDF]

				L. Cervenka, V. Horacek, I. Vaneckova, J. A. Hubacek, M. I. Oliverio, T. M. Coffman, and L. G. Navar Essential Role of AT1A Receptor in the Development of 2K1C Hypertension Hypertension, November 1, 2002; 40(5): 735 - 741. [Abstract] [Full Text] [PDF]