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  3. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents)
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Volume 23, Issue 1
  • ISSN: 1871-5257
  • E-ISSN: 1875-6182

Abstract

Background

Pulmonary Hypertension (PH) leads to changes in pulmonary vascular architecture, hypertrophy of the right ventricle, and heart failure. Sildenafil is a drug that can modulate PH by inducing smooth muscle relaxation and vasodilation.

Aims

To investigate the ability of sildenafil to alleviate the monocritaline (MCT)-induced PH in rats and to estimate the role and its effect on the atrial natriuretic peptide (ANP) levels.

Methods

28 adult male rats were divided randomly into four groups: Group A (control group; n=7). Group B (MCT-treated group; n=7) was given a single dose of MCT 60 mg/kg subcutaneously. Group C (The reversal group; n=7) received a single dose of MCT 60 mg/kg subcutaneously for three weeks and then sildenafil at 50 mg/kg/day, given daily for another three weeks. Group D (The prevention group; n=7) simultaneously received a single dose of MCT 60 mg/kg subcutaneously and sildenafil daily at 50 mg/kg for three weeks.

Results

The animals in the prevention group showed a significant decrease in ANP levels compared to the reversal and MCT-treated groups. This decrease was associated with a significant reduction in the Fulton index ratio in the prevention group compared to the reversal group. The nitric oxide levels were also significantly higher in the reversal group than in the control group.

Conclusion

Preventive sildenafil treatment was associated with a significant decrease in ANP levels and reduced MCT-induced cardiac hypertrophy in rats.

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2025-05-05

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References

  1. WalkerB.R. ColledgeN.R. Davidson’s principles and practice of medicine London.UKElsevier Health Sciences2016
     [Google Scholar]
  2. GalièN. GhofraniH.A. TorbickiA. BarstR.J. RubinL.J. BadeschD. FlemingT. ParpiaT. BurgessG. BranziA. GrimmingerF. KurzynaM. SimonneauG. Sildenafil citrate therapy for pulmonary arterial hypertension.N. Engl. J. Med.2005353202148215710.1056/NEJMoa05001016291984
     [Google Scholar]
  3. BarnettC.F. MachadoR.F. Sildenafil in the treatment of pulmonary hypertension.Vasc. Health Risk Manag.20062441142210.2147/vhrm.2006.2.4.41117323595
     [Google Scholar]
  4. TakimotoE. ChampionH.C. LiM. BelardiD. RenS. RodriguezE.R. BedjaD. GabrielsonK.L. WangY. KassD.A. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy.Nat. Med.200511221422210.1038/nm117515665834
     [Google Scholar]
  5. RubinL.J. BadeschD.B. FlemingT.R. GalièN. SimonneauG. GhofraniH.A. OakesM. LaytonG. Serdarevic-PeharM. McLaughlinV.V. BarstR.J. Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: The SUPER-2 study.Chest201114051274128310.1378/chest.10‑096921546436
     [Google Scholar]
  6. Gomez-ArroyoJ.G. FarkasL. AlhussainiA.A. FarkasD. KraskauskasD. VoelkelN.F. BogaardH.J. The monocrotaline model of pulmonary hypertension in perspective.Am. J. Physiol. Lung Cell. Mol. Physiol.20123024L363L36910.1152/ajplung.00212.201121964406
     [Google Scholar]
  7. ReidM.J. LaméM.W. MorinD. WilsonD.W. SegallH.J. Involvement of cytochrome P450 3A in the metabolism and covalent binding of 14C-monocrotaline in rat liver microsomes.J. Biochem. Mol. Toxicol.199812315716610.1002/(SICI)1099‑0461(1998)12:3<157::AID‑JBT4>3.0.CO;2‑K9522275
     [Google Scholar]
  8. Silva-NetoJ.P. BarretoR.A. PitangaB.P.S. SouzaC.S. SilvaV.D. SilvaA.R. VelozoE.S. CunhaS.D. BatatinhaM.J.M. TardyM. RibeiroC.S.O. CostaM.F.D. El-BacháR.S. CostaS.L. Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells.Toxicon201055110511710.1016/j.toxicon.2009.07.00719615397
     [Google Scholar]
  9. KayJ.M. HarrisP. HeathD. Pulmonary hypertension produced in rats by ingestion of Crotalaria spectabilis seeds.Thorax196722217617910.1136/thx.22.2.1766033385
     [Google Scholar]
  10. HandokoM.L. de ManF.S. HappéC.M. SchalijI. MustersR.J.P. WesterhofN. PostmusP.E. PaulusW.J. van der LaarseW.J. Vonk-NoordegraafA. Opposite effects of training in rats with stable and progressive pulmonary hypertension.Circulation20091201424910.1161/CIRCULATIONAHA.108.82971319546388
     [Google Scholar]
  11. LaméM.W. JonesA.D. WilsonD.W. SegallH.J. Monocrotaline pyrrole targets proteins with and without cysteine residues in the cytosol and membranes of human pulmonary artery endothelial cells.Proteomics20055174398441310.1002/pmic.20040202216222722
     [Google Scholar]
  12. KimJ. HwangboC. HuX. KangY. PapangeliI. MehrotraD. ParkH. JuH. McLeanD.L. ComhairS.A. ErzurumS.C. ChunH.J. Restoration of impaired endothelial myocyte enhancer factor 2 function rescues pulmonary arterial hypertension.Circulation2015131219019910.1161/CIRCULATIONAHA.114.01333925336633
     [Google Scholar]
  13. PotterL.R. Abbey-HoschS. DickeyD.M. Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions.Endocr. Rev.2006271477210.1210/er.2005‑001416291870
     [Google Scholar]
  14. de BoldA.J. Functional-morphological studies on in vitro cardionatrin release.J. Hypertens. Suppl.198642S3S7
     [Google Scholar]
  15. EdwardsB.S. ZimmermanR.S. SchwabT.R. HeubleinD.M. BurnettJ.C. Jr Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor.Circ. Res.198862219119510.1161/01.RES.62.2.1912962782
     [Google Scholar]
  16. ChanJ.C.Y. KnudsonO. WuF. MorserJ. DoleW.P. WuQ. Hypertension in mice lacking the proatrial natriuretic peptide convertase corin.Proc. Natl. Acad. Sci. USA2005102378579010.1073/pnas.040723410215637153
     [Google Scholar]
  17. MukoyamaM. NakaoK. HosodaK. SugaS. SaitoY. OgawaY. ShirakamiG. JougasakiM. ObataK. YasueH. Brain natriuretic peptide as a novel cardiac hormone in humans. Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide.J. Clin. Invest.19918741402141210.1172/JCI1151461849149
     [Google Scholar]
  18. HagiwaraH. SakaguchiH. ItakuraM. YoshimotoT. FuruyaM. TanakaS. HiroseS. Autocrine regulation of rat chondrocyte proliferation by natriuretic peptide C and its receptor, natriuretic peptide receptor-B.J. Biol. Chem.199426914107291073310.1016/S0021‑9258(17)34119‑47908295
     [Google Scholar]
  19. DrewettJ.G. GarbersD.L. The family of guanylyl cyclase receptors and their ligands.Endocr. Rev.199415213516210.1210/edrv‑15‑2‑1357913014
     [Google Scholar]
  20. KollerK.J. LoweD.G. BennettG.L. MinaminoN. KangawaK. MatsuoH. GoeddelD.V. Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP).Science1991252500212012310.1126/science.16727771672777
     [Google Scholar]
  21. CannoneV. CabassiA. VolpiR. BurnettJ.C. Jr Atrial natriuretic peptide: A molecular target of novel therapeutic approaches to cardio-metabolic disease.Int. J. Mol. Sci.20192013326510.3390/ijms2013326531269783
     [Google Scholar]
  22. Marin-GrezM. FlemingJ.T. SteinhausenM. Atrial natriuretic peptide causes pre-glomerular vasodilatation and post-glomerular vasoconstriction in rat kidney.Nature1986324609647347610.1038/324473a02946962
     [Google Scholar]
  23. BabaM. YoshidaK. IedaM. Clinical applications of natriuretic peptides in heart failure and atrial fibrillation.Int. J. Mol. Sci.20192011282410.3390/ijms2011282431185605
     [Google Scholar]
  24. BaligaR.S. ZhaoL. MadhaniM. Lopez-TorondelB. VisintinC. SelwoodD. WilkinsM.R. MacAllisterR.J. HobbsA.J. Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension.Am. J. Respir. Crit. Care Med.2008178886186910.1164/rccm.200801‑121OC18689467
     [Google Scholar]
  25. AdnotS. ChabrierP.E. AndrivetP. ViossatI. PiquetJ. Brun-BuissonC. GutkowskaY. BraquetP. Atrial natriuretic peptide concentrations and pulmonary hemodynamics in patients with pulmonary artery hypertension.Am. Rev. Respir. Dis.1987136495195610.1164/ajrccm/136.4.9512959183
     [Google Scholar]
  26. WiedemannR. GhofraniH.A. WeissmannN. SchermulyR. QuanzK. GrimmingerF. SeegerW. OlschewskiH. Atrial natriuretic peptide in severe primary and nonprimary pulmonary hypertension.J. Am. Coll. Cardiol.20013841130113610.1016/S0735‑1097(01)01490‑511583893
     [Google Scholar]
  27. SirmagulB. IlginS. AtliO. UsanmazS.E. Demirel-YilmazE. Assessment of the endothelial functions in monocrotaline-induced pulmonary hypertension.Clin. Exp. Hypertens.201335322022710.3109/10641963.2012.72183822967272
     [Google Scholar]
  28. SchermulyR.T. KreisselmeierK.P. GhofraniH.A. YilmazH. ButrousG. ErmertL. ErmertM. WeissmannN. RoseF. GuentherA. WalmrathD. SeegerW. GrimmingerF. Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats.Am. J. Respir. Crit. Care Med.20041691394510.1164/rccm.200302‑282OC12958054
     [Google Scholar]
  29. BaeH.K. LeeH. KimK.C. HongY.M. The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure.Korean J. Pediatr.201659626227010.3345/kjp.2016.59.6.26227462355
     [Google Scholar]
  30. HardziyenkaM. CampianM.E. Rianne de Bruin-BonH.A.C.M. MichelM.C. TanH.L. Sequence of echocardiographic changes during development of right ventricular failure in rat.J. Am. Soc. Echocardiogr.200619101272127910.1016/j.echo.2006.04.03617000367
     [Google Scholar]
  31. Chamsi-PashaH. Sildenafil (Viagra) and the heart.J. Family Community Med.200182636610.4103/2230‑8229.9918923008645
     [Google Scholar]
  32. ZhaoL. MasonN.A. MorrellN.W. KojonazarovB. SadykovA. MaripovA. MirrakhimovM.M. AldashevA. WilkinsM.R. Sildenafil inhibits hypoxia-induced pulmonary hypertension.Circulation2001104442442810.1161/hc2901.09311711468204
     [Google Scholar]
  33. OhieT. KikuchiK. WatanabeK. MoriC. Cardiac atrial natriuretic peptide in monocrotaline‐induced pulmonary hypertensive rats.Pediatr. Int.199335427828210.1111/j.1442‑200X.1993.tb03053.x8379317
     [Google Scholar]
  34. SchäferS. EllinghausP. JanssenW. KramerF. LustigK. MiltingH. KastR. KleinM. Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling.Cardiovasc. Res.2009821303910.1093/cvr/cvp00219131365
     [Google Scholar]
  35. PrestonI.R. HillN.S. GambardellaL.S. WarburtonR.R. KlingerJ.R. Synergistic effects of ANP and sildenafil on cGMP levels and amelioration of acute hypoxic pulmonary hypertension.Exp. Biol. Med. (Maywood)2004229992092510.1177/15353702042290090815388887
     [Google Scholar]
  36. MathewR. YuanN. RosenfeldL. GewitzM.H. KumarA. Effects of monocrotaline on endothelial nitric oxide synthase expression and sulfhydryl levels in rat lungs.Heart Dis.20024315215810.1097/00132580‑200205000‑0000412028599
     [Google Scholar]
  37. XueC. JohnsR.A. Endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension.N. Engl. J. Med.1995333241642164410.1056/NEJM1995121433324167477212
     [Google Scholar]
  38. MasonN.A. SpringallD.R. BurkeM. PollockJ. MikhailG. YacoubM.H. PolakJ.M. High expression of endothelial nitric oxide synthase in plexiform lesions of pulmonary hypertension.J. Pathol.1998185331331810.1002/(SICI)1096‑9896(199807)185:3<313::AID‑PATH93>3.0.CO;2‑89771486
     [Google Scholar]
  39. CoolC.D. StewartJ.S. WeraheraP. MillerG.J. WilliamsR.L. VoelkelN.F. TuderR.M. Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth.Am. J. Pathol.1999155241141910.1016/S0002‑9440(10)65137‑110433934
     [Google Scholar]
  40. KhatibS. AlJinabiM. Abstract 2500: The effect of sildenafil on atrial natriuretic peptide level in rats treated with monocrotaline.J. Biol. Chem.2023299310443810.1016/j.jbc.2023.104438
     [Google Scholar]
/content/journals/chamc/10.2174/0118715257293794240516075211
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Sildenafil Effect on Atrial Natriuretic Peptide Level in Pulmonary Hypertensive Rats
Cardiovasc. Hematol. Agents Med. Chem. 23, 69 (2025); https://doi.org/10.2174/0118715257293794240516075211
/content/journals/chamc/10.2174/0118715257293794240516075211
/content/journals/chamc/10.2174/0118715257293794240516075211
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  • Article Type:     Research Article
Keyword(s): atrial natriuretic peptide; MCT; monocrotaline; nitric oxide; Pulmonary hypertension; sildenafil

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