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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 394, Issue 9

Issues

ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries

Kathryn M. Gauthier / Cody J. Cepura / William B. Campbell
Published Online: 2013-05-29 | DOI: https://doi.org/10.1515/hsz-2012-0348

Abstract

Bradykinin causes vascular relaxations through release of endothelial relaxing factors including prostacyclin, nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). Bradykinin is metabolized by angiotensin converting enzyme (ACE) and ACE inhibition enhances bradykinin relaxations. Our goal was to characterize the role of bradykinin receptors and endothelial factors in ACE inhibitor-enhanced relaxations in bovine coronary arteries. In U46619 preconstricted arteries, bradykinin (10-11-10-8m) caused concentration-dependent relaxations (maximal relaxation ≥100%, log EC50=-9.8±0.1). In the presence of the NO synthase inhibitor, N-nitro-L-arginine (L-NA, 30 μm) and the cyclooxygenase inhibitor, indomethacin (10 μm), relaxations were reduced by an inhibitor of EET synthesis, miconazole (10 μm) (maximal relaxation=55±10%). Bradykinin relaxations were inhibited by the bradykinin 2 (B2) receptor antagonist, D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin (1 μm) (log EC50=-8.5±0.1) but not altered by the B1 receptor antagonist, des-Arg9[Leu8]bradykinin (1 μm). Mass spectrometric analysis of bovine coronary artery bradykinin metabolites revealed a time-dependent increase in bradykinin (1–5) and (1–7) suggesting metabolism by ACE. ACE inhibition with captopril (50 μm) enhanced bradykinin relaxations (log EC50=-10.3±0.1). The enhanced relaxations were eliminated by L-NA or the B1 receptor antagonist but not the B2 receptor antagonist. Our results demonstrate that ACE inhibitor-enhanced bradykinin relaxations of bovine coronary arteries occur through endothelial cell B1 receptor activation and NO.

Keywords: bradykinin receptors; captopril; endothelium; epoxyeicosatrienoic acids

References

  • Baudin, B., Berard, M., Carrier, J.L., Legrand, Y., and Drouet, L. (1997). Vascular origin determines angiotensin I-converting enzyme expression in endothelial cells. Endothelium 5, 73–84.Web of ScienceGoogle Scholar

  • Beril, T., Dendorfer, A., de Vries, R., Saxena, P.R., and Danser, A.H.J. (2002). Bradykinin potentiation by ACE inhibitors: a matter of metabolism. Br. J. Pharmacol. 137, 276–284.Google Scholar

  • Bujak-Giżycka, B., Olszanecki, R., Madej, J., Suski, M., Gębska, A., and Korbut, R. (2011). Metabolism of bradykinin in aorta of hypertensive rats. Acta. Biochim. Pol. 58, 199–202.Google Scholar

  • Campbell, W.B., Gebremedhin, D., Pratt, P.F., and Harder, D.R. (1996). Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors. Circ. Res. 78, 415–423.Google Scholar

  • Campbell, W.B., Falck, J.R., and Gauthier, K.M. (2001). Role of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factor in bovine coronary arteries. Med. Sci. Monit. 7, 578–584.Google Scholar

  • Cockcroft, J.R., Chowienczyk, P.J., Brett, S.E., Bender, N., and Ritter J.M. (1994). Inhibition of bradykinin-induced vasodilation in human forearm vasculature by icatibant, a potent B2-receptor antagonist. Br. J. Clin. Pharmacol. 38, 317–321.Google Scholar

  • Cui, L., Nithipatikom, K., and Campbell, W.B. (2007). Simultaneous analysis of angiotensin peptides by LC-MS and LC-MS/MS: metabolism by bovine adrenal endothelial cells. Anal. Biochem. 369, 27–33.Web of ScienceGoogle Scholar

  • Drummond, G.R. and Cocks, T.M. (1995). Endothelium-dependent relaxation to the B1 kinin receptor agonist des-Arg9-bradykinin in human coronary arteries. Br. J. Pharmacol. 116, 3083–3085.Google Scholar

  • Erdös, E.G., Tan, F., and Skidgel, R.A. (2010). Angiotensin I-converting enzyme inhibitors are allosteric enhancers of kinin B1 and B2 receptor function. Hypertension 55, 214–220.Google Scholar

  • Ferreira, S.H. and Vane, J.R. (1967). The disappearance of bradykinin and eledoisin in the circulation and vascular beds of the cat. Br. J. Pharmacol. Chemother. 30, 417–424.Google Scholar

  • Figueroa, C.D., Marchant, A., Novoa, U., Förstermann, U., Jarnagin, K., Schölkens, B., and Müller-Esterl, W. (2001). Differential distribution of bradykinin B(2) receptors in the rat and human cardiovascular system. Hypertension 37, 110–120.Google Scholar

  • Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D.R., Fleming, I., and Busse, R. (1999). Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401, 493–497.Google Scholar

  • Gauthier, K.M., Deeter, C., Krishna, U.M., Reddy, Y.K., Bondlela, M., Falck, J.R., and Campbell, W.B. (2002). 14,15-Epoxyeicosa-5(Z)-enoic acid: A selective epoxyeicosatrienoic acid antagonist that inhibits endothelium-dependent hyperpolarization and relaxation in coronary arteries. Circ. Res. 90, 1028–1036.Google Scholar

  • Gauthier, K.M., Edwards, E.M., Falck, J.R., Reddy, D.S., and Campbell, W.B. (2005). 14,15-Epoxyeicosatrienoic acid represents a transferable endothelium-dependent relaxing factor in bovine coronary arteries. Hypertension 45, 666–671.Google Scholar

  • Gauthier, K.M., Zhang, D.X., Cui, L., Nithipatikom, K., and Campbell, W.B. (2008). Angiotensin II relaxations of bovine adrenal cortical arteries: role of angiotensin II metabolites and endothelial nitric oxide. Hypertension 52, 150–155.Web of ScienceGoogle Scholar

  • Gebremedhin, D., Harder, D.R., Pratt, P.F., and Campbell, W.B. (1998). Bioassay of an endothelium-derived hyperpolarizing factor from bovine coronary arteries: role of a cytochrome P450 metabolite. J. Vasc. Res. 35, 274–284.Google Scholar

  • Hall, J.M. (1992). Bradykinin receptors: Pharmacological properties and biological roles. Pharmacol. Ther. 56, 131–190.Google Scholar

  • Ignjatovic, T., Stanisavljevic, S., Brovkovych, V., Skidgel, R.A., and Erdös, E.G. (2004). Kinin B1 receptors stimulate nitric oxide production in endothelial cells: signaling pathways activated by angiotensin I-converting enzyme inhibitors and peptide ligands. Mol. Pharmacol. 66, 1310–1316.Google Scholar

  • Koller, A., Rodenburg, J.M., and Kaley, G. (1995). Effects of Hoe-140 and ramiprilat on arteriolar tone and dilation to bradykinin in skeletal muscle of rats. Am. J. Physiol. Heart Circ. Physiol. 268, H1628–H1633.Google Scholar

  • Marceau, F. and Regoli, D. (2004). Bradykinin receptor ligands: therapeutic perspectives. Nat. Rev. Drug Discov. 3, 845–852.Google Scholar

  • Marceau, F., Hess, F., and Bachvarov, D.R. (1998). The B1 Receptors for Kinins. Pharmacol. Rev. 50, 357–386.Google Scholar

  • McLean, P.G., Perretti, M., and Ahluwalia, A. (2000). Kinin B1 receptors and the cardiovascular system: regulation of expression and function. Cardiovasc. Res. 48, 194–210.Google Scholar

  • Miyamoto, A., Ishiguro, S., and Nishio, A. (1999). Stimulation of bradykinin B2-receptors on endothelial cells induces relaxation and contraction in porcine basilar artery in vitro. Br. J. Pharmacol. 128, 241–247.Google Scholar

  • Mombouli, J.V., Illiano, S., Nagao, T., Scott-Burden, T., and Vanhoutte, P.M. (1992). Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors. Circ. Res. 71, 137–44.Google Scholar

  • Mombouli, J.V., Ballard, K.D., and Vanhoutte, P.M. (2002). Kininase-independent potentiation of endothelium-dependent relaxations to kinins by converting enzyme inhibitor perindoprilat. Acta. Pharmacol. Sin. 23, 203–207.Google Scholar

  • Murphey, L.J., Hachey, D.L., Oates, J.A., Morrow, J.D., and Brown, N.J. (2000). Metabolism of bradykinin in vivo in humans: Identification of BK1-5 as a stable plasma peptide metabolite. J. Pharmacol. Exp. Ther. 294, 263–269.Google Scholar

  • Passos, G.F., Fernandes, E.S., Campos, M.M., Araújo, J.G., Pesquero, J.L., Souza, G.E., Avellar, M.C., Teixeira, M.M., and Calixto, J.B. (2004). Kinin B1 receptor up-regulation after lipopolysaccharide administration: role of proinflammatory cytokines and neutrophil influx. J. Immunol. 172, 1839–1847.Google Scholar

  • Pratt, P.F., Rosolowsky, M., and Campbell, W.B. (1996). Mediators of arachidonic acid-induced relaxation of bovine coronary artery. Hypertension 28, 76–82.Google Scholar

  • Pratt, P.F., Li, P., Hillard, C.J., Kurian, J., and Campbell, W.B. (2001). Endothelium-independent, ouabain-sensitive relaxation of bovine coronary arteries by EETs. Am. J. Physiol. Heart Circ. Physiol. 280, H1113–H1121.Google Scholar

  • Pruneau, D., Luccarini, J-M., Defrêne, E., Paquet, J-L., and Bélichard, P. (1996). Characterisation of bradykinin receptors from juvenile pig coronary artery. Eur. J. Pharmacol. 297, 53–60.Google Scholar

  • Ren, Y., Garvin, J., and Carretero, O.A. (2002). Mechanism involved in bradykinin-induced efferent arteriole dilation. Kidney Int. 62, 544–549.Google Scholar

  • Skeggs, L.T. Jr., Kahn, J.R., and Shumway, N.P. (1956). The preparation and function of the hypertensin-converting enzyme. J. Exper. Med. 103, 295–299.Google Scholar

  • Skidgel, R.A., Stanisavljevic, S., and Erdös, E.G. (2006). Kinin- and angiotensin-converting enzyme (ACE) inhibitor-mediated nitric oxide production in endothelial cells. Biol. Chem. 387, 159–165.Google Scholar

  • Smith, W.H. and Ball, S.G. (2000). ACE inhibitors in heart failure: an update. Basic Res. Cardiol. 95, 8–14.Google Scholar

  • Stanisavljevic, S., Ignjatovic, T., Deddish, P.A., Brovkovych, V., Zhang, K., Erdös, E.G., and Skidgel, R.A. (2006). Angiotensin I-converting enzyme inhibitors block protein kinase C by activating bradykinin B1 receptors in human endothelial cells. J. Pharmacol. Exp. Ther. 316, 1153–1158.Google Scholar

  • Su, J.B., Hoüel, R., Héloire, F., Barbe, F., Beverelli, F., Sambin, L., Castaigne, A., Berdeaux, A., Crozatier, B., and Hittinger, L. (2000). Stimulation of bradykinin B1 receptors induces vasodilation in conductance and resistance coronary vessels in conscious dogs: Comparison with B2 receptor stimulation. Circulation 101, 1848–1853.Google Scholar

  • Yang, H.Y., Erdös, E.G., and Levin, Y. (1971). Characterization of a dipeptide hydrolase (kininase II: angiotensin I converting enzyme). J. Pharmacol. Exp. Ther. 177, 291–300.Google Scholar

  • Zhang, X., Tan, F., Brovkovych, V., Zhang, Y., and Skidgel, R.A. (2011). Cross-talk between carboxypeptidase M and the kinin B1 receptor mediates a new mode of G protein-coupled receptor signaling. J. Biol. Chem. 286, 18547–18561.Google Scholar

About the article

Corresponding author: Kathryn M. Gauthier, Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA


Received: 2012-12-06

Accepted: 2013-05-16

Published Online: 2013-05-29

Published in Print: 2013-09-01


Citation Information: Biological Chemistry, Volume 394, Issue 9, Pages 1205–1212, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0348.

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