Abstract
Sarafotoxin-i3 from Atractaspis irregularis is a long sarafotoxin with an extended C terminus extension. Sarafotoxin-b from Atractaspis engaddensis is shorter by four amino acids. These peptides belong to the endothelin-like peptide family with a high sequence homology and similar three-dimensional structure. They act on endothelin receptors situated on the membrane of endothelial and smooth muscle cells. However, SRTX-i 3, despite a high toxicity, has a very low affinity for endothelin receptors compared to SRTX-b. The present work was carried out in order to compare the precise in vivo cardiovascular effect of SRTX-b and SRTX-i3. Male Wistar rats were anesthetized and mechanically ventilated. Doppler echocardiography was performed to measure left and right ventricular functions. The rats were divided into three groups that received intravenous injections of: saline, SRTX-b or SRTX-i3. All measurements were taken at baseline, at 1 min and at 6 min after injection. Both toxins impaired cardiac output. SRTX-b impaired left ventricular function, while SRTX-i3 increased airway pressures and led to acute right ventricular dilatation associated with a decreased tricuspid annulus peak systolic velocity. SRTX-b and SRTX-i3 appear to exert toxic effects via different mechanisms, SRTX-b impairs left ventricular function, while SRTX-i3 increases airway pressures and impairs right ventricular function.
Abbreviations
- SRTXs:
-
Sarafotoxins
- SRTX-b:
-
Sarafotoxin-b extracted from the venom of Atractaspis engaddensis
- SRTX-i3:
-
Sarafotoxin-i3 extracted from the venom of Atractaspis irregularis
- ET-A:
-
Endothelin-receptor subtype A
- ET-B:
-
Endothelin-receptor subtype B
- LV:
-
Left ventricle
- RV:
-
Right ventricle
- LVFA:
-
Left ventricular fractional area
- LVEDA:
-
Left ventricular end-diastolic area
- RVEDA:
-
Right ventricular end-diastolic area
- CO:
-
Cardiac output
- SV:
-
Stroke volume
- S′:
-
Tricuspid annulus peak systolic velocity
References
Ducancel, F. (2005). Endothelin-like peptides. Cellular and Molecular Life Sciences: CMLS, 62(23), 2828–2839. doi:10.1007/s00018-005-5286-x.
Sokolovsky, M. (1991). Endothelins and sarafotoxins: Physiological regulation, receptor subtypes and transmembrane signaling. Trends in Biochemical Sciences, 16(7), 261–264.
Ducancel, F. (2002). The sarafotoxins. Toxicon, 40(11), 1541–1545.
Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., et al. (1988). A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature, 332(6163), 411–415. doi:10.1038/332411a0.
Wollberg, Z., Shabo-Shina, R., Intrator, N., Bdolah, A., Kochva, E., Shavit, G., et al. (1988). A novel cardiotoxic polypeptide from the venom of Atractaspis engaddensis (burrowing asp): Cardiac effects in mice and isolated rat and human heart preparations. Toxicon, 26(6), 525–534.
Quinton, L., Le Caer, J.-P., Phan, G., Ligny-Lemaire, C., Bourdais-Jomaron, J., Ducancel, F., et al. (2005). Characterization of toxins within crude venoms by combined use of Fourier transform mass spectrometry and cloning. Analytical Chemistry, 77(20), 6630–6639. doi:10.1021/ac050575k.
Mourier, G., Hajj, M., Cordier, F., Zorba, A., Gao, X., Coskun, T., et al. (2012). Pharmacological and structural characterization of long-sarafotoxins, a new family of endothelin-like peptides: Role of the C-terminus extension. Biochimie, 94(2), 461–470. doi:10.1016/j.biochi.2011.08.014.
Mahjoub, Y., Malaquin, S., Mourier, G., Lorne, E., Abou Arab, O., Massy, Z. A., et al. (2015). Short- versus long-sarafotoxins: Two structurally related snake toxins with very different in vivo haemodynamic effects. PLoS One, 10(7), e0132864. doi:10.1371/journal.pone.0132864.
Mourier, G., Dutertre, S., Fruchart-Gaillard, C., Ménez, A., & Servent, D. (2003). Chemical synthesis of MT1 and MT7 muscarinic toxins: critical role of Arg-34 in their interaction with M1 muscarinic receptor. Molecular Pharmacology, 63(1), 26–35.
Pacher, P., Nagayama, T., Mukhopadhyay, P., Bátkai, S., & Kass, D. A. (2008). Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats. Nature Protocols, 3(9), 1422–1434. doi:10.1038/nprot.2008.138.
Tei, C., Nishimura, R. A., Seward, J. B., & Tajik, A. J. (1997). Noninvasive Doppler-derived myocardial performance index: Correlation with simultaneous measurements of cardiac catheterization measurements. Journal of the American Society of Echocardiography, 10(2), 169–178.
Bdolah, A., Wollberg, Z., Ambar, I., Kloog, Y., Sokolovsky, M., & Kochva, E. (1989). Disturbances in the cardiovascular system caused by endothelin and sarafotoxin. Biochemical Pharmacology, 38(19), 3145–3146.
Han, S. P., Knuepfer, M. M., Trapani, A. J., Fok, K. F., & Westfall, T. C. (1990). Cardiac and vascular actions of sarafotoxin S6b and endothelin-1. Life Sciences, 46(11), 767–775.
Jardin, F., Dubourg, O., & Bourdarias, J. P. (1997). Echocardiographic pattern of acute cor pulmonale. Chest, 111(1), 209–217.
Meluzín, J., Spinarová, L., Bakala, J., Toman, J., Krejcí, J., Hude, P., et al. (2001). Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion; a new, rapid, and non-invasive method of evaluating right ventricular systolic function. European Heart Journal, 22(4), 340–348. doi:10.1053/euhj.2000.2296.
Kurnik, D., Haviv, Y., & Kochva, E. (1999). A snake bite by the Burrowing Asp, Atractaspis engaddensis. Toxicon, 37(1), 223–227.
Khimji, A.-K., & Rockey, D. C. (2010). Endothelin: Biology and disease. Cellular Signalling, 22(11), 1615–1625. doi:10.1016/j.cellsig.2010.05.002.
D’Orléans-Juste, P., Labonté, J., Bkaily, G., Choufani, S., Plante, M., & Honoré, J. C. (2002). Function of the endothelin(B) receptor in cardiovascular physiology and pathophysiology. Pharmacology and Therapeutics, 95(3), 221–238.
Konrad, D., Oldner, A., Wanecek, M., Rudehill, A., Weitzberg, E., Biber, B., et al. (2005). Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo. American Journal of Physiology. Heart and Circulatory Physiology, 289(4), H1702–H1709. doi:10.1152/ajpheart.00892.2004.
Repessé, X., Charron, C., & Vieillard-Baron, A. (2013). Evaluation of left ventricular systolic function revisited in septic shock. Critical Care (London, England), 17(4), 164. doi:10.1186/cc12755.
Atkins, A. R., Martin, R. C., & Smith, R. (1995). 1H NMR studies of sarafotoxin SRTb, a nonselective endothelin receptor agonist, and IRL 1620, an ETB receptor-specific agonist. Biochemistry, 34(6), 2026–2033.
Vieillard-Baron, A., Loubieres, Y., Schmitt, J. M., Page, B., Dubourg, O., & Jardin, F. (1999). Cyclic changes in right ventricular output impedance during mechanical ventilation. Journal of Applied Physiology (Bethesda, Md.: 1985), 87(5), 1644–1650.
Fukuroda, T., Ozaki, S., Ihara, M., Ishikawa, K., Yano, M., Miyauchi, T., et al. (1996). Necessity of dual blockade of endothelin ETA and ETB receptor subtypes for antagonism of endothelin-1-induced contraction in human bronchi. British Journal of Pharmacology, 117(6), 995–999.
Nagase, T., Aoki, T., Matsui, H., Ohga, E., Katayama, H., Teramoto, S., et al. (1997). Airway and lung tissue behaviour during endothelin-1 induced constriction in rats: Effects of receptor antagonists. Canadian Journal of Physiology and Pharmacology, 75(12), 1369–1374.
Leite, S., Pinto, J. O., Silva, M. T., Abdellatif, M., Fontoura, D., Falcão-Pires, I., et al. (2015). Echocardiography and invasive hemodynamics during stress testing for diagnosis of heart failure with preserved ejection fraction: An experimental study. American Journal of Physiology. Heart and Circulatory Physiology,. doi:10.1152/ajpheart.00076.2015.
Slama, M., Ahn, J., Peltier, M., Maizel, J., Chemla, D., Varagic, J., et al. (2005). Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats. American journal of physiology. Heart and circulatory physiology, 289(3), H1131–H1136. doi:10.1152/ajpheart.00345.2004.
Kimura, K., Daimon, M., Morita, H., Kawata, T., Nakao, T., Okano, T., et al. (2015). Evaluation of right ventricle by speckle tracking and conventional echocardiography in rats with right ventricular heart failure. International Heart Journal, 56(3), 349–353. doi:10.1536/ihj.14-367.
Acknowledgments
We thank Prof. Michel Slama (Medical intensive care unit, CHU Amiens) for his helpful advices and Dr. Denis Servent (SIMOPRO-CEA-Saclay) for the participation of his research group.
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Mahjoub, Y., Malaquin, S., Abou Arab, O. et al. Echocardiographic Evaluation of the Acute Cardiovascular Effects of an Endothelin-Like Peptide Extracted from the Venom of Atractaspis irregularis . Cardiovasc Toxicol 17, 208–214 (2017). https://doi.org/10.1007/s12012-016-9376-9
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DOI: https://doi.org/10.1007/s12012-016-9376-9