Leptin Enhances Nitric Oxide Production and Decreases Blood Flow in Rat Skeletal Muscle

Yıl 2022, Cilt: 81 Sayı: 1, 18 - 25, 30.06.2022

Savaş Üstünova , Ayşegül Kapucu , Cihan Demirci Tansel

https://doi.org/10.26650/EurJBiol.2022.1082814

Öz

Objective: There are a few studies related to nitric oxide (NO) and leptin interaction in the regulation of physiological events in skeletal muscle. Therefore, the aim of the present study is to investigate the interaction of leptin and NO in response to blood flow and nitric oxide synthase (NOS) distribution on rat skeletal muscle. Materials and Methods: Twenty-four adult-male Wistar albino rats were divided into 4 groups: control (C), Leptin (LP) (50 μg/kg), L-NG-nitroarginine methyl ester (LN) (a non-specific nitric oxide synthase inhibitor, 10 mg/kg,) and L-NAME+Leptin (LN+LP) administrated groups. Drugs were administered via the right jugular vein. Hemodynamic parameters: mean arterial pressure, heart rate and blood flow were recorded during the experiment and at the end blood samples for biochemical analyses of leptin and nitrite/nitrate levels and gastrocnemius muscle tissues from the right hindlimb for NOS distribution were taken. Results: Leptin infusion after L-NAME administration significantly decreased heart rate and blood flow (p<0.05, p<0.001). In addition, there was no change in the mean arterial pressure in the leptin group and leptin-administered L-NAME group. Leptin levels were the highest in the LP+LN group (p<0.01). Decreased nitrate/nitrate levels with L-NAME administration (p<0.01 vs C) reached control values by leptin infusion. Both endothelial NOS (eNOS) and neuronal NOS (nNOS) distributions were observed in the skeletal muscle cells of the leptin group. Conclusion: Although NO synthesis is inhibited by L-NAME, it is concluded that leptin partially enhances NO production and leptin uses NO as a mediator in its physiological effects.

Anahtar Kelimeler

Blood flow, leptin, nitric oxide, rat; skeletal muscle

Proje Numarası

T-744/13092005

Kaynakça

• 1. Paz-Filho G, Mastronardi CA, Licinio J. Leptin treatment: facts and xpectations. Metabolism 2015; 64(1): 146-56. 2. Zhang Y, Chua S, Jr. Leptin Function and Regulation. Compr Physiol 2017; 8(1): 351-69.
• 3. Kokta TA, Dodson MV, Gertler A, Hill RA. Intercellular signaling between adipose tissue and muscle tissue. Domest Anim Endocrinol 2004; 27(4): 303-31.
• 4. Sletten AC, Peterson LR, Schaffer JE. Manifestations and mechanisms of myocardial lipotoxicity in obesity. J Intern Med 2018; 284(5): 478-91.
• 5. Minokoshi Y, Toda C, Okamoto S. Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle. Indian J Endocrinol Metab 2012; 16(Suppl 3): S562.
• 6. Ciriello J. Leptin in nucleus of the solitary tract alters the cardiovascular responses to aortic baroreceptor activation. Peptides 2013; 44: 1-7.
• 7. Smith PM, Ferguson AV. Cardiovascular actions of leptin in the subfornical organ are abolished by diet‐induced obesity. J Neuroendocrinol 2012; 24(3): 504-10.
• 8. Hassan MJM, Bakar NS, Aziz MA, Basah NK, Singh HJ. Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin, a marinobufagenin antagonist. Reprod Biol 2020; 20(2): 184-90.
• 9. Rahmouni K, Jalali A, Morgan DA, Haynes WG. Lack of dilator effect of leptin in the hindlimb vascular bed of conscious rats. Eur J Pharmacol 2005; 518(2-3): 175-81.
• 10. Winters B, Mo Z, Brooks-Asplund E, Kim S, Shoukas A, Li D, et al. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lepob) mice. J Appl Physiol 2000; 89(6): 2382-90.
• 11. Robbins RA, Grisham MB. Nitric oxide. Int J Biochem Cell Biol 1997; 29(6): 857-60.
• 12. Buchwalow IB, Minin EA, Samoilova VE, Boecker W, Wellner M, Schmitz W, et al. Compartmentalization of NO signaling cascade in skeletal muscles. Biochem Biophys Res Commun 2005; 330(2): 615-21.
• 13. Grozdanovic Z. NO message from muscle. Microsc Res Tech 2001; 55(3): 148-53.
• 14. Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev 2001; 81(1): 209-37.
• 15. Frühbeck G. Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 1999; 48(4): 903-8.
• 16. Fuhrich DG, Lessey BA, Savaris RF. Comparison of HSCORE assessment of endometrial beta3 integrin subunit expression with digital HSCORE using computerized image analysis (ImageJ). Anal Quant Cytopathol Histpathol 2013; 35(4): 210-6.
• 17. Arneth W, Herold B. Nitrate nitrite determination in sausages after enzymatic reduction. Fleischwirtschaft 1988; 68(6): 761-4.
• 18. Goshi E, Zhou G, He Q. Nitric oxide detection methods in vitro and in vivo. Med Gas Res 2019; 9(4): 192.
• 19. Ren J. Leptin and hyperleptinemia-from friend to foe for cardiovascular function. J Endocrinol 2004; 181(1): 1-10.
• 20. Castracane VD, Henson MC. Leptin. Endocrine Updates: Springer; 2006.
• 21. Correia MLG, Morgan DA, Sivitz WI, Mark AL, Haynes WG. Leptin acts in the central nervous system to produce dose-dependent changes in arterial pressure. Hypertension 2001; 37(3): 936-42.
• 22. Bełtowski J, Jochem J, Wójcicka G, Żwirska-Korczala K. Influence of intravenously administered leptin on nitric oxide production, renal hemodynamics and renal function in the rat. Regul Pept 2004; 120(1-3): 59-67.
• 23. Mitchell JL, Morgan DA, Correia MLG, Mark AL, Sivitz WI, Haynes WG. Does leptin stimulate nitric oxide to oppose the effects of sympathetic activation? Hypertension 2001; 38(5): 1081-6.
• 24. Dunbar JC, Hu Y, Lu H. Intracerebroventricular leptin increases lumbar and renal sympathetic nerve activity and blood pressure in normal rats. Diabetes 1997; 46(12): 2040-3.
• 25. Bełtowski J, Wójcicka G, Jamroz-Wiśniewska A. Role of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the regulation of blood pressure by leptin in lean and obese rats. Life Sci 2006; 79(1): 63-71.
• 26. Kang K-W, Ok M, Lee S-K. Leptin as a key between obesity and cardiovascular disease. Journal of Obesity & Metabolic Syndrome 2020; 29(4): 248.
• 27. Jamroz-Wiśniewska A, Gertler A, Solomon G, Wood ME, Whiteman M, Bełtowski J. Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide. PLoS One 2014; 9(1): e86744.
• 28. Simonds SE, Pryor JT, Cowley MA. Does leptin cause an increase in blood pressure in animals and humans? Current opinion in nephrology and hypertension 2017; 26(1): 20-5.
• 29. Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, d’Amati G, et al. Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 2000; 49(2): 293-7.
• 30. Frühbeck G, Gómez-Ambrosi J. Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide. Cell Signal 2001; 13(11): 827-33.
• 31. Mastronardi CA, Yu WH, McCann SM. Resting and circadian release of nitric oxide is controlled by leptin in male rats. Proc Natl Acad Sci 2002; 99(8): 5721-6.
• 32. Sweeney G. Leptin signalling. Cell Signal 2002; 14(8): 655-63.
• 33. Brevetti LS, Chang DS, Tang GL, Sarkar R, Messina LM. Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia. J Vasc Surg 2003; 38(4): 820-6.
• 34. Punkt K, Naupert A, Wellner M, Asmussen G, Schmidt C, Buchwalow IB. Nitric oxide synthase II in rat skeletal muscles. Histochem Cell Biol 2002; 118(5): 371-9.
• 35. Punkt K, Zaitsev S, Park JK, Wellner M, Buchwalow IB. Nitric oxide synthase isoforms I, III and protein kinase-Cθ in skeletal muscle fibres of normal and streptozotocin-induced diabetic rats with and without Ginkgo biloba extract treatment. Histochem J 2001; 33(4): 213-9.
• 36. Vranić TS, Bobinac D, Jurisić-Erzen D, Muhvić D, Sandri M, Jerković R. Expression of neuronal nitric oxide synthase in fast rat skeletal muscle. Coll Antropol 2002; 26: 183-8.
• 37. Yan Z, Chen Z. Modulation of nitric oxide synthase isoenzymes in reperfused skeletal muscle. Chin J Traumatol 2000; 3(2): 76-80.
• 38. Carbó N, Ribas V, Busquets S, Alvarez B, López-Soriano FJ, Argilés JM. Short-term effects of leptin on skeletal muscle protein metabolism in the rat. J Nutr Biochem 2000; 11(9): 431-5.