Effect of Central and Peripheral Injected Nesfatin-1 on Electrocardiography in Rats

Year 2019, Volume: 38 Issue: 1, 10 - 17, 18.07.2019

Kubra Cıftcı Gokcen Guvenc Aysenur Bas Murat Yalcın

https://doi.org/10.30782/uluvfd.445316

Abstract

Nesfatin-1 is an anorexic nucleobindin-2 -derived peptide and it has directly and centrally effect on the heart. The current study was designed

to determine the effect of centrally and peripherally administered nesfatin-1 on electrocardiography (ECG) of healthy both fasted rats for 12

h and satiated rats fed ad libitum. In order to record ECG, the electrodes were placed limbs of at lead II under ketamine (50 mg/kg; im) and

xylazine (20 mg/kg; im) anesthesia mix.

Centrally administered different doses of nesfatin-1 (100 and 200 pmol; icv) resulted in dose- and time-dependently a statistically significant

increase (p <0.05) in T wave, Q-T interval, and R-R interval duration without changing in ECG waves’ amplitude in both satiated and fasted

rats. In a similar way, peripheral administration of nesfatin-1 (80 μg/kg; iv) in satiated rats prolonged statistically significant (p <0.05) T wave,

Q-T interval, and R-R interval without producing a change in ECG waves’ amplitude. Moreover, icv administered nesfatin-1 in fasted and

satiated rats, and iv injected nesfatin-1 in satiated rats induced a statistically significant decrease in heart rate (p <0.05).

In conclusion, our findings suggest that centrally and peripherally administrated nesfatin-1 caused a delay in T wave, Q-T interval and two

R-waves interval duration in ECG so that leading to a bradycardic effect in heart rate.

Keywords

Nesfatin-1, Electrocardiography, Intracerebroventricular, Intravenous, Heart rate

References

• 1. Oh-I S, Shimizu H, Satoh T, et al. Identification of nesfatin- 1 as a satiety molecule in the hypothalamus. Nature. 2006;12:709–712.
• 2. Brailoiu GC, Dun SL, Brailoiu E, et al. Nesfatin-1: distribution and interaction with a G protein-coupled receptor in the rat brain. Endocrinology. 2007;148:5088– 5094.
• 3. Goebel M, Stengel A, Wang L, et al. Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett. 2009;452:241–246.
• 4. Stengel A, Goebel M, Yakubov I, et al. Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa. Endocrinology. 2009;150:232–238.
• 5. Angelone T, Filice E, Pasqua T, et al. Nesfatin-1 as a novel cardiac peptide: identification, functional characterization, and protection against ischemia/reperfusion injury. Cell Mol Life Sci. 2013;70:495–509.
• 6. Garcia-Galiano D, Navarro VM, Gaytan F, et al. Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation. J Mol Endocrinol. 2010;45:281–290.
• 7. Stengel A, Tache Y. Minireview: nesfatin-1--an emerging new player in the brain-gut, endocrine, and metabolic axis. Endocrinology. 2011;152:4033-4038.
• 8. Yilmaz MS, Altinbas B, Guvenc G, et al. The role of centrally injected nesfatin-1 on cardiovascular regulation in normotensive and hypotensive rats. Auton Neurosci. 2015;193:63–68.
• 9. Aydin B, Guvenc G, Altinbas B, et al. Modulation of nesfatin-1-induced cardiovascular effects by the central cholinergic system. Neuropeptides. 2018;70:9-15.
• 10. Tanida M, Mori M. Nesfatin-1 stimulates renal sympathetic nerve activity in rats. Neuroreport. 2011;20:309– 312.
• 11. Yosten GL, Samson WK. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Phys Regul Integr Comp Phys. 2009;297:330–336.
• 12. Mimee A, Smith PM, Ferguson AV. Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function. Am J Phys Regul Integr Comp Phys. 2012;302:1297– 1304.
• 13. Yamawaki H, Takahashi M, Mukohda M, et al. A novel adipocytokine, nesfatin-1 modulates peripheral arterial contractility and blood pressure in rats. Biochem Biophys Res Commun. 2012;24:676–681.
• 14. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 4th Ed. Academic Press, New York; 2005.
• 15. Hall JE. Cardiac Arrhythmias and their electrocardiographic interpretation. In: Hall JE, Guyton AC, Schmitt W, eds. Guyton and Hall Textbook of Medical Physiology. 12th ed. Saunders, London; 2011:143-153.
• 16. Wagner GS, Macfarlane P, Wellens H, et al. AHA/ ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part VI: acute ischemia/infarction: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol. 2009;53:1003-1011.
• 17. Brailoiu GC, Deliu E, Tica AA, et al. Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguous and elicits bradycardia in conscious rats. J Neurochem. 2013;126:739–748.
• 18. Yosten GL, Samson WK. The anorexigenic and hypertensive effects of nesfatin-1 are reversed by pretreatment with an oxytocin receptor antagonist. Am J Phys Regul Integr Comp Phys. 2010;298:1642–1647.
• 19. Yosten GL, Samson WK. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin. Am J Phys Regul Integr Comp Phys. 2014;306:722–727.
• 20. Kohno D, Nakata M, Maejima Y, et al. Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat hypothalamus coexpress oxytocin and vasopressin and are activated by refeeding. Endocrinology. 2008;149:1295–1301.