Role of nitric oxide in septal coronary arteries of obese Zucker rats

  • Authors

    • Priyanka Prathipati ULM College of Pharmacy
    • Syed Quadri ULM College of Pharmacy
    • Debra Jackson ULM Department of Biology
    • Keith Jackson ULM College of Pharmacy
    2014-03-25
    https://doi.org/10.14419/ijm.v2i1.1941
  • Background: Metabolic syndrome is a collection of ailments resulting in a higher risk of cardiovascular disease and type II diabetes mellitus. It also results in prolonged endothelial dysfunction which promotes hypertension.

    Objective: The current study examines the acute effect of carbon monoxide (CO) inhibition and nitric oxide (NO) stimulation in septal coronary arteries.

    Methods: These studies were conducted in inactin anesthetized obese and lean Zucker rats (13-14 weeks of age). Coronary arteries were isolated from obese and lean Zucker rats and in vitro experiments were conducted.  Isolated coronary arteries were pre-treated with chromium mesoporphyrin (CrMP) which is a heme oxygenase inhibitor and L-arginine, a NO precursor.

    Results: Blood pressure, non-fasting blood glucose, HBCO, CO levels and Arginase I expression were higher in obese Zucker rats (ZR) as compared to the lean (L) group. Obese ZR had higher body, kidney and heart weights as compared to the LZR. Acetylcholine induced vasodilation was greatly attenuated in Obese ZR compared to the lean group. No differences in the diameters of the septal coronary artery were observed in both groups when treated with CrMP. However, pretreatment with L-arginine, abolished the differences between the groups.

    Conclusion: This study demonstrates the potential of NO induction to improve coronary blood flow during metabolic syndrome induced endothelial dysfunction, where alterations in CO levels appeared to have no significant coronary effects.

     

    Keywords: Metabolic Syndrome, Endothelial Dysfunction, Hypertension, L-Arginine, Endogenous CO.

  • References

    1. Ford ES, Giles WH, & Dietz WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287, 356-359.
    2. Ford ES, Li C, & Zhao G (2010) Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US. J Diabetes 2, 180-193.
    3. Alessi MC & Juhan (2008) Vague I: Metabolic syndrome, haemostasis and thrombosis. Thromb Haemost 99, 995-1000.
    4. Stehouwer CD, Henry RM, & Ferreira I (2008) Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia 51, 527-539.
    5. Kasiske BL, O Donnell MP, & Keane WF (1992) The Zucker rat model of obesity, insulin resistance, hyperlipidemia and renal injury. Hypertension 19, 110-115.
    6. Frisbee JC & Stepp DW (2001) Impaired NO-dependant dilation of skeletal muscle arterioles in hypertensive obese Zucker rats. Am J Physiol Heart Circ Physiol 281, H1304-H1311.
    7. Durham HA & Truett GE (2006) Development of insulin resistance and hyperphagia in Zucker fatty rats. Am J Physiol Regul Interg Comp Physiol 210, R652-658.
    8. Shafrir E & Ziv E (2009) A useful list of spontaneously arising animal models of obesity and diabetes. Am J Physiol Endocrinol Metab 296, E1450-E1452.
    9. Srinivasan K & Ramarao P (2007) Animal models in type 2 diabetes research: an overview. Indian J Med Res 125, 451-472.
    10. Jarmi T & Agarwal A (2009) Heme oxygenase and renal disease. Curr Hypertens Rep 11, 56-62.
    11. Tenhunen R, Marver HS & Schmid R (1969) Microsomal heme oxygenase. Characterization of the enzyme. J Biol Chem 244, 6388-6394.
    12. Tenhunen R (1976) The enzymatic conversion of heme to bilirubin in vivo. Ann Clin Res 8, 2-9.
    13. Maines MD (1997) The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37, 517-554.
    14. Abraham NG & Kappas A (2005) Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med 39, 1-25.
    15. Sabaawy HE, Zhang F, Nguyen X, Elhosseiny A, Nasjletti A, Schwartzman M, Dennery P, Kappas A & Abraham NG (2001) Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats. Hypertension 38, 210-215.
    16. Juan SH, Lee TS, Tseng KW, Liou JY, Shyue SK, Wu K & Chau LY (2001) Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 104, 1519-1525.
    17. Tang YL, Qian K, Zhang YC, Shen L & Phillips MI (2005) A vigilant, hypoxia- regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo. J Cardiovasc Pharmacol Ther 10, 251-263.
    18. Furchgott RF & Jothianandan D (1991) Endothelium-dependent and -independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide, carbon monoxide and light. Blood Vessels 28, 52-61.
    19. Stec DE, Drummond HA, & Vera T (2008) Role of carbon monoxide in blood pressure regulation. Hypertension 51, 597-604.
    20. Durante W & Schafer Al (1998) Carbon monoxide and vascular cell function (review). Int J Mol Med 2, 255-262.
    21. Johnson FK, Johnson RA, Durante W, Jackson KE, Stevenson BK, & Peyton KJ (2006) Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 290, R601-608.
    22. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, & Schillaci G (2001) Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 104, 191-196.
    23. Andreas J, Flammer T, & Luscher F (2010) Three decades of endothelium research: from the detection of nitric oxide to the everyday implementation of endothelial function measurements in cardiovascular diseases. Swiss Medical Weekly 140, w13122.
    24. Shantsila E, Shantsila A, Blann AD, & Lip GY (2013) Left Ventricular Fibrosis in Atrial Fibrillation. Am J Cardiol 111, 996-1001.
    25. Johnson FK & Johnson RA (2003) Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles. Am J Physiol Regul Integr Comp Physiol 285, R536-541.
    26. White KA & Marletta MA (1992) Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry 31, 6627-6631.
    27. Thorup C, Jones CL, Gross SS, Moore LC, & Goligorsky MS (1992) Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am J Physiol 277, F882-889.
    28. Strijdom H, Chamane N, & Lochner A (2009) Nitric oxide in the cardiovascular system: a simple molecule with complex actions. Cardiovasc J Afr 20, 303-310.
    29. Vanhoutte PM & Gao Y (2013) Beta blockers, nitric oxide, and cardiovascular disease. Curr Opin Pharmacol 13, 265-273.
    30. Sárközy M, Zvara A, Gyémánt N, Fekete V, Kocsis GF, Pipis J, Sz CG, Csonka C, Puskás LG, Ferdinandy P, & Csont T (2013) Metabolic syndrome influences cardiac gene expression pattern at the transcript level in male ZDF rats. Cardiovasc Diabetol 12, 16-32.
    31. Ming XF, Barandier C, Viswambharan H, Kwak BR, Mach F, Mazzolai L, Hayoz D, Rusconi S, Montani JP, & Yang Z (2004) Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction. Circulation 110, 3708-3714.
    32. Vreman HJ, Knauer Y, Wong RJ, Chan ML, & Stevenson DK (2009) Dermal carbon monoxide excretion in neonatal rats during light exposure. Pediatr Res 66, 66-69.
    33. Jackson KE, Jackson DW, Quadri S, Reitzell MJ, & Navar LG (2011) Inhibition of heme oxygenase augments tubular sodium reabsorption. Am J Physiol Renal Physiol 300, F941-F946.
    34. Vreman HJ, Wong RJ, Kadotani T, & Stevenson DK (2005) Determination of carbon monoxide (CO) in rodent tissue: effect of heme administration and environmental CO exposure. Anal Biochem 341, 280-289.
    35. Sun D, Kaley G, & Koller A (1994) Characteristics and origin of myogenic response in isolated gracilis muscle arterioles. Am J Physiol 266, H1177-1183.
    36. Kozma F, Johnson RA, Zhang F, Yu C, Tong X, & Nasjletti A (1999) Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels. Am J Physiol 276, R1087-1094.
    37. Berkowitz DE, White R, Li D, Mihas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, & Hare JM (2003) Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 108, 2000-2006.
    38. Durante W, Johnson FK, & Johnson RA (2007) Arginase: a critical regulator of nitric oxide synthesis and vascular function. Clin Exp Pharmacol Physiol 34, 906-911.
    39. Kohli R, Meininger CJ, Haynes TE, Yan W, Self JT, & Wu G (2004) Dietary L-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J Nutr 134, 600-608.
    40. Cylwik D, Mogielnicki A, & Buczko W (2005) L-arginine and cardiovascular system. Pharmacol Rep 57, 14-22.
  • Downloads

    Additional Files

  • How to Cite

    Prathipati, P., Quadri, S., Jackson, D., & Jackson, K. (2014). Role of nitric oxide in septal coronary arteries of obese Zucker rats. International Journal of Medicine, 2(1), 8-12. https://doi.org/10.14419/ijm.v2i1.1941