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Model difference in the effect of cilostazol on the development of experimental pulmonary hypertension in rats

Ito Toshikazu 三重大学

2022.07.20

概要

Background: Preventing pulmonary vascular remodeling is a key strategy for pulmonary hypertension (PH). Causes of PH include pulmonary vasoconstriction and inflammation. This study aimed to determine whether cilostazol (CLZ), a phosphodiesterase-3 inhibitor, prevents monocrotaline (MCT)- and chronic hypoxia (CH)-induced PH development in rats.
Methods: Fifty-one male Sprague–Dawley rats were fed rat chow with (0.3% CLZ) or without CLZ for 21 days after a single injection of MCT (60mg/kg) or saline. Forty-eight rats were fed rat chow with and without CLZ for 14 days under ambient or hypobaric (air at 380 mmHg) CH exposure. The mean pulmonary artery pressure (mPAP), the right ventricle weight-to-left ventricle + septum weight ratio (RV/LV + S), percentages of muscularized peripheral pulmonary arteries (%Muscularization) and medial wall thickness of small muscular arteries (%MWT) were assessed. Levels of the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (peNOS), AKT, pAKT and IκB proteins in lung tissue were measured using Western blotting. Monocyte chemotactic protein (MCP)-1 mRNA in lung tissue was also assessed.
Results: mPAP [35.1±1.7 mmHg (MCT) (n=9) vs. 16.6±0.7(control) (n=9) (P < 0.05); 29.1± 1.5 mmHg(CH)(n=10)vs. 17.5±0.5(control)(n=10)(P<0.05)], RV/LV+S[0.40±0.01(MCT)(n=18) vs. 0.24±0.01(control)(n=10)(P<0.05); 0.41±0.03(CH)(n=13) vs. 0.27± 0.06 (control)(n=10)(p<0.05)], and %Muscularization and %MWT were increased by MCT injection and CH exposure. CLZ significantly attenuated these changes in the MCT model [mPAP25.1±1.1 mmHg(n=11) (P<0.05), RV/LV+S 0.30±0.01(n=14) (P < 0.05)]. In contrast, these CLZ effects were not observed in the CH model. Lung eNOS protein expression was unchanged in the MCT model and increased in the CH model. Lung protein expression of AKT, phosphorylated AKT, and IκB was downregulated by MCT, which was attenuated by CLZ; the CH model did not change these proteins. Lung MCP-1 mRNA levels were increased in MCT rats but not CH rats.
Conclusions: We found model differences in the effect of CLZ on PH development. CLZ might exert a preventive effect on PH development in an inflammatory PH model but not in a vascular structural change model of PH preceded by vasoconstriction. Thus, the preventive effect of CLZ on PH development might depend on the PH etiology.

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参考文献

1. Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation. 2010;121:2045–66.

2. Rabinovitch M. Molecular pathogenesis of pulmonary arterial hyperten- sion. J Clin Investig. 2008;118:2372–9.

3. Rabinovitch M, Keane JF, Norwood WI, Castaneda AR, Reid L. Vascular structure in lung tissue obtained at biopsy correlated with pulmonary hemodynamic findings after repair of congenital heart defects. Circula- tion. 1984;69:655–67.

4. Snow RL, Davies P, Pontoppidan H, Zapol WM, Reid L. Pulmonary vascular remodeling in adult respiratory distress syndrome. Am Rev Respir Dis. 1982;126:887–92.

5. Tomashefski JF Jr, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983;112:112–26.

6. Mitani Y, Maruyama K, Sakurai M. Prolonged administration of L-arginine ameliorates chronic pulmonary hypertension and pulmonary vascular remodeling in rats. Circulation. 1997;96:689–97.

7. Kouyoumdjian C, Adnot S, Levame M, Eddahibi S, Bousbaa H, Raffestin B. Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats. J Clin Investig. 1994;94:578–84.

8. Ye CL, Rabinovitch M. Inhibition of elastolysis by SC-37698 reduces devel- opment and progression of monocrotaline pulmonary hypertension. Am J Physiol. 1991;261:H1255–67.

9. Zhang E, Maruyama J, Yokochi A, Mitani Y, Sawada H, Nishikawa M, Ma N, Maruyama K. Sarpogrelate hydrochloride, a serotonin 5HT2A receptor antagonist, ameliorates the development of chronic hypoxic pulmonary hypertension in rats. J Anesth. 2015;29:715–23.

10. Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L. Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features. Am J Physiol. 1979;236:H818–27.

11. Maruyama K, Ye CL, Woo M, Venkatacharya H, Lines LD, Silver MM, Rabinovitch M. Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity. Am J Physiol. 1991;261:H1716–26.

12. Maruyama J, Maruyama K, Mitani Y, Kitabatake M, Yamauchi T, Miyasaka K. Continuous low-dose NO inhalation does not prevent monocrotaline-induced pulmonary hypertension in rats. Am J Physiol. 1997;272:H517–24.

13. Ilkiw R, Todorovich-Hunter L, Maruyama K, Shin J, Rabinovitch M. SC-39026, a serine elastase inhibitor, prevents muscularization of peripheral arteries, suggesting a mechanism of monocrotaline-induced pulmonary hypertension in rats. Circ Res. 1989;64:814–25.

14. Yamada Y, Maruyama J, Zhang E, Okada A, Yokochi A, Sawada H, Mitani Y, Hayashi T, Suzuki K, Maruyama K. Effect of thrombomodulin on the devel- opment of monocrotaline-induced pulmonary hypertension. J Anesth. 2014;28:26–33.

15. Meyrick B, Gamble W, Reid L. Development of Crotalaria pulmonary hypertension: hemodynamic and structural study. Am J Physiol. 1980;239:H692-702.

16. Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: the hope for etiological discov- ery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol. 2009;297:L1013–32.

17. Hill NS, Warburton RR, Pietras L, Klinger JR. Nonspecific endothelin-recep- tor antagonist blunts monocrotaline-induced pulmonary hypertension in rats. J Appl Physiol. 1997;83:1209–15.

18. Schermuly RT, Kreisselmeier KP, Ghofrani HA, Yilmaz H, Butrous G, Ermert L, Ermert M, Weissmann N, Rose F, Guenther A, Walmrath D, Seeger W, Grimminger F. Chronic sildenafil treatment inhibits monocrotaline- induced pulmonary hypertension in rats. Am J Respir Crit Care Med. 2004;169:39–45.

19. Eddahibi S, Raffestin B, Clozel M, Levame M, Adnot S. Protection from pulmonary hypertension with an orally active endothelin receptor antagonist in hypoxic rats. Am J Physiol. 1995;268:H828–35.

20. Zhao L, Mason NA, Morrell NW, Kojonazarov B, Sadykov A, Maripov A, Mir- rakhimov MM, Aldashev A, Wilkins MR. Sildenafil inhibits hypoxia-induced pulmonary hypertension. Circulation. 2001;104:424–8.

21. Zapol WM, Snider MT. Pulmonary hypertension in severe acute respira- tory failure. N Engl J Med. 1977;296:476–80.

22. Maruyama K, Nakai Y, Takeuchi M, Mizumoto T, Chikusa H, Muneyuki M. Verapamil reduced pulmonary hypertension in adult respiratory distress syndrome. J Anesth. 1994;8:480–1.

23. Maruyama K, Takeuchi M, Chikusa H, Muneyuki M. Reduction of intrapul- monary shunt by low-dose inhaled nitric oxide in a patient with late- stage respiratory distress associated with paraquat poisoning. Intensive Care Med. 1995;21:778–9.

24. Maruyama K, Maruyama J, Utsunomiya H, Furuhashi K, Kurobuchi M, Katayama Y, Yada I, Muneyuki M. Effect of nicardipine on pulmonary hypertension after repair of congenital heart defects in early postopera- tive period. J Anesth. 1993;7:95–101.

25. Shimpo H, Mitani Y, Tanaka J, Mizumoto T, Onoda K, Tani K, Yuasa H, Yada I, Maruyama K. Inhaled low-dose nitric oxide for postoperative care in patients with congenital heart defects. Artif Organs. 1997;21:10–3.

26. Breitling S, Ravindran K, Goldenberg NM, Kuebler WM. The pathophysiol- ogy of pulmonary hypertension in left heart disease. Am J Physiol Lung Cell Mol Physiol. 2015;309:L924–41.

27. Maruyama K, Kobayasi H, Taguchi O, Chikusa H, Muneyuki M. Higher doses of inhaled nitric oxide might be less effective in improving oxy- genation in a patient with interstitial pulmonary fibrosis. Anesth Analg. 1995;81:210–1.

28. Zamanian RT, Haddad F, Doyle RL, Weinacker AB. Management strategies for patients with pulmonary hypertension in the intensive care unit. Crit Care Med. 2007;35:2037–50.

29. Goldenberg NM, Rabinovitch M, Steinberg BE. Inflammatory basis of pul- monary arterial hypertension: implications for perioperative and critical care medicine. Anesthesiology. 2019;131:898–907.

30. Klinger JR, Kadowitz PJ. The nitric oxide pathway in pulmonary vascular disease. Am J Cardiol. 2017;120:S71–9.

31. Maruyama J, Jiang BH, Maruyama K, Takata M, Miyasaka K. Prolonged nitric oxide inhalation during recovery from chronic hypoxia does not decrease nitric oxide-dependent relaxation in pulmonary arteries. Chest. 2004;126:1919–25.

32. Maruyama J, Maruyama K. Impaired nitric oxide-dependent responses and their recovery in hypertensive pulmonary arteries of rats. Am J Physiol. 1994;266:H2476–88.

33. Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res. 2005;96:442–50.

34. Hiatt WR. The US experience with cilostazol in treating intermittent claudication. Atheroscler Suppl. 2005;6:21–31.

35. Tsuchikane E, Fukuhara A, Kobayashi T, Kirino M, Yamasaki K, Kobayashi T, Izumi M, Otsuji S, Tateyama H, Sakurai M, Awata N. Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty. Circulation. 1999;100:21–6.

36. Noma K, Higashi Y. Cilostazol for treatment of cerebral infarction. Expert Opin Pharmacother. 2018;19:1719–26.

37. Suzuki K, Uchida K, Nakanishi N, Hattori Y. Cilostazol activates AMP-acti- vated protein kinase and restores endothelial function in diabetes. Am J Hypertens. 2008;21:451–7.

38. Hashimoto A, Miyakoda G, Hirose Y, Mori T. Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/protein kinase A- and phos- phatidylinositol 3-kinase/Akt-dependent mechanism. Atherosclerosis. 2006;189:350–7.

39. Ikeda U, Ikeda M, Kano S, Kanbe T, Shimada K. Effect of cilostazol, a cAMP phosphodiesterase inhibitor, on nitric oxide production by vascular smooth muscle cells. Eur J Pharmacol. 1996;314:197–202.

40. Hassan M, Ibrahim MA, Hafez HM, Mohamed MZ, Zenhom NM, Abd Elghany HM. Role of Nrf2/HO-1 and PI3K/Akt genes in the hepatoprotec- tive effect of cilostazol. Curr Clin Pharmacol. 2019;14:61–7.

41. Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflam- mation and infection. Annu Rev Immunol. 2011;29:139–62.

42. Sakamoto T, Ohashi W, Tomita K, Hattori K, Matsuda N, Hattori Y. Anti- inflammatory properties of cilostazol: its interruption of DNA binding activity of NF-κB from the Toll-like receptor signaling pathways. Int Immunopharmacol. 2018;62:120–31.

43. Chang LT, Sun CK, Sheu JJ, Chiang CH, Youssef AA, Lee FY, Wu CJ, Yip HK. Cilostazol therapy attenuates monocrotaline-induced pulmonary arterial hypertension in rat model. Circ J. 2008;72:825–31.

44. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62:D34-41.

45. Sawada H, Mitani Y, Maruyama J, Jiang BH, Ikeyama Y, Dida FA, Yamamoto H, Imanaka-Yoshida K, Shimpo H, Mizoguchi A, Maruyama K, Komada Y. A nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate ameliorates pulmonary hypertension in rats. Chest. 2007;132:1265–74.

46. Dai M, Xiao R, Cai L, Ge T, Zhu L, Hu Q. HMGB1 is mechanistically essential in the development of experimental pulmonary hypertension. Am J Physiol Cell Physiol. 2019;316:C175–85.

47. Qin Y, Zhou A, Ben X, et al. All-trans retinoic acid in pulmonary vascular structural remodeling in rats with pulmonary hypertension induced by monocrotaline. Chin Med J. 2001;114:462–5.

48. Rosenberg HC, Rabinovitch M. Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension. Am J Physiol. 1988;255:H1484–91.

49. Voelkel NF, Tuder RM, Bridges J, Arend WP. Interleukin-1 receptor antago- nist treatment reduces pulmonary hypertension generated in rats by monocrotaline. Am J Respir Cell Mol Biol. 1994;11:664–75.

50. Kimura H, Kasahara Y, Kurosu K, Sugito K, Takiguchi Y, Terai M, Mikata A, Natsume M, Mukaida N, Matsushima K, Kuriyama T. Alleviation of mono- crotaline-induced pulmonary hypertension by antibodies to monocyte chemotactic and activating factor/monocyte chemoattractant protein-1. Lab Investig. 1998;78:571–81.

51. Le Cras TD, Xue C, Renqasamy A, et al. Chronic hypoxia upregulates endothelial and inducible NO synthase gene and protein expression in rat lung. Am J Physiol. 1996;270:L164-170.

52. Otsuka Pharmaceutical Co. LTD. Standard Commondity Classification Number of Japan 873399. PLETAAL OD Tablets 50mg·100mg, Medical attachment, HD89D2B01, 2019

53. Rabinovitch M, Gamble WJ, Miettinen OS, Reid L. Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery. Am J Physiol. 1981;240:H62-72.

54. Kimura T, Hamazaki TS, Sugaya M, Fukuda S, Chan T, Tamura-Nakano M, Sato S, Okochi H. Cilostazol improves lymphatic function by inducing proliferation and stabilization of lymphatic endothelial cells. J Dermatol Sci. 2014;74:150–8.

55. Zhang XP, Hintze TH. cAMP signal transduction induces eNOS activation by promoting PKB phosphorylation. Am J Physiol Heart Circ Physiol. 2006;290:H2376–84.

56. Kim HN, Gil CH, Kim YR, Shin HK, Choi BT. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice. Sci Rep. 2016;6:31169.

57. Tyler RC, Muramatsu M, Abman SH, et al. Variable expression of endothe- lial NO synthase in three forms of rat pulmonary hypertension. Am J Physiol. 1999;276:L297-303.

58. Kawabe-Yako R, Ii M, Masuo O, Asahara T, Itakura T. Cilostazol acti- vates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model. PLoS ONE. 2011;6:e24646.

59. Jung WK, Lee DY, Park C, Choi YH, Choi I, Park SG, Seo SK, Lee SW, Yea SS, Ahn SC, Lee CM, Park WS, Ko JH, Choi IW. Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear factor-kappaB and inhibit- ing mitogen-activated protein kinases. Br J Pharmacol. 2010;159:1274–85.

60. Park WS, Jung WK, Lee DY, Moon C, Yea SS, Park SG, Seo SK, Park C, Choi YH, Kim GY, Choi JS, Choi IW. Cilostazol protects mice against endotoxin shock and attenuates LPS-induced cytokine expression in RAW 264.7 macrophages via MAPK inhibition and NF-kappaB inactivation: not involved in cAMP mechanisms. Int Immunopharmacol. 2010;10:1077–85.

61. Beg AA, Finco TS, Nantermet PV, Baldwin AS Jr. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol. 1993;13:3301–10.

62. Chang KC. Cilostazol inhibits HMGB1 release in LPS-activated RAW 264.7 cells and increases the survival of septic mice. Thromb Res. 2015;136:456–64.

63. O’Kane CM, Elkington PT, Jones MD, Caviedes L, Tovar M, Gilman RH, Stamp G, Friedland JS. STAT3, p38 MAPK, and NF-kappaB drive unop- posed monocyte-dependent fibroblast MMP-1 secretion in tuberculosis. Am J Respir Cell Mol Biol. 2010;43:465–74.

64. Yu BC, Lee DS, Bae SM, Jung WK, Chun JH, Urm SH, Lee DY, Heo SJ, Park SG, Seo SK, Yang JW, Choi JS, Park WS, Choi IW. The effect of cilostazol on the expression of matrix metalloproteinase-1 and type I procollagen in ultraviolet-irradiated human dermal fibroblasts. Life Sci. 2013;92:282–8.

65. Nakamura K, Hatano E, Miyagawa-Hayashino A, Okuno M, Koyama Y, Narita M, Seo S, Taura K, Uemoto S. Soluble thrombomodulin attenuates sinusoidal obstruction syndrome in rat through suppression of high mobility group box 1. Liver Int. 2014;34:1473–87.

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