This Article Full Text Full Text (PDF) All Versions of this Article: 42/5/1021    most recent 01.HYP.0000097550.98865.35v1 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 Duka, I. Articles by Gavras, H. Search for Related Content PubMed PubMed Citation Articles by Duka, I. Articles by Gavras, H. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB INDOMETHACIN Related Collections Gene expression Hypertension - basic studies Endothelium/vascular type/nitric oxide

(Hypertension. 2003;42:1021.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Mechanisms Mediating the Vasoactive Effects of the B₁ Receptors of Bradykinin

Irena Duka; Arvi Duka; Ekaterina Kintsurashvili; Conrado Johns; Irene Gavras; Haralambos Gavras

From the Hypertension and Atherosclerosis Section of the Department of Medicine, Boston University School of Medicine, Boston, Mass.

Correspondence to Haralambos Gavras, MD, FRCP, Chief, Hypertension and Atherosclerosis Section, Boston University School of Medicine, 715 Albany St, Boston, MA 02118. E-mail hgavras{at}bu.edu

Bradykinin normally exerts its vasodilatory effect via the B₂ receptor (B₂R), but in this receptor’s absence, the B₁ receptor becomes expressed and activated. To explore the mechanism of B₁R-mediated vasodilation, 8 groups of B₂R gene–knockout mice received a 2-week infusion of a B₁R antagonist (300 µg · kg^-1 · d^-1) or vehicle (groups 1 and 2), B₁R antagonist or vehicle plus NO inhibition with N-nitro-L-arginine methyl ester (groups 3 and 4), B₁R antagonist or vehicle plus cyclooxygenase inhibition with indomethacin (groups 5 and 6), or B₁R antagonist or vehicle plus blockade of vasoconstricting prostaglandin (PG) H₂ and thromboxane A₂ (TxA₂) with SQ29548 (groups 7 and 8). The B₁R antagonist produced significant (P<0.05) blood pressure increases of 17.7±3.1 mm Hg in group 1 and 10.4±3 mm Hg in group 3, whereas their vehicle-treated respective control groups 2 and 4 had no significant blood pressure changes. Indomethacin abolished the capacity of the B₁R antagonist to raise blood pressure, as did blockade of the receptors of PGH₂ and TxA₂. Injection with the B₁R agonist produced a hypotensive response (12±1.3 mm Hg), which was further accentuated by TxA₂ blockade (21.7±4.1 mm Hg). Analysis of B₁R gene expression by reverse transcription–polymerase chain reaction (PCR) in cardiac and renal tissues revealed marked expression at baseline, with further upregulation by 1.5- to 2-fold after various manipulations. Expression of the TxA₂ receptor gene in renal tissue by quantitative real-time PCR was significantly lower in mice treated with the B₁R antagonist, consistent with increased levels of agonist for this receptor. The data confirm that the B₁R becomes markedly expressed in the absence of B₂R and suggest that it contributes to vasodilation by inhibiting a vasoconstricting product of the arachidonic acid cascade acting via the PGH₂/TxA₂ receptor.

Key Words: receptors, bradykinin • mice • nitric oxide • prostaglandins • vasorelaxation

This article has been cited by other articles:

				J. Xu, O. A. Carretero, E. G. Shesely, N.-E. Rhaleb, J. J. Yang, M. Bader, and X.-P. Yang The kinin B1 receptor contributes to the cardioprotective effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in mice Exp Physiol, March 1, 2009; 94(3): 322 - 329. [Abstract] [Full Text] [PDF]

				A. Duka, E. Kintsurashvili, I. Duka, D. Ona, T. A. Hopkins, M. Bader, I. Gavras, and H. Gavras Angiotensin-Converting Enzyme Inhibition After Experimental Myocardial Infarct: Role of the Kinin B1 and B2 Receptors Hypertension, May 1, 2008; 51(5): 1352 - 1357. [Abstract] [Full Text] [PDF]

				S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio, D. Hayoz, B. Pannier, C. Vlachopoulos, I. Wilkinson, H. Struijker-Boudier, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications Eur. Heart J., November 1, 2006; 27(21): 2588 - 2605. [Abstract] [Full Text] [PDF]

				A. Duka, I. Duka, G. Gao, S. Shenouda, I. Gavras, and H. Gavras Role of bradykinin B1 and B2 receptors in normal blood pressure regulation Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E268 - E274. [Abstract] [Full Text] [PDF]

				E. Kintsurashvili, A. Duka, I. Ignjacev, G. Pattakos, I. Gavras, and H. Gavras Age-related changes of bradykinin B1 and B2 receptors in rat heart Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H202 - H205. [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]