The impact of phosphodiesterase-5 inhibition or angiotensin-converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload.
heart failure
phosphodiesterase-5 inhibition
rats
right ventricle
volume overload
Journal
Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
revised:
19
12
2023
received:
18
10
2023
accepted:
20
12
2023
medline:
29
1
2024
pubmed:
29
1
2024
entrez:
29
1
2024
Statut:
ppublish
Résumé
While phosphodiesterase-5 inhibition (PED5i) may prevent hypertrophy and failure in pressure-overloaded heart in an experimental model, the impact of PDE5i on volume-overload (VO)-induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long-term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto-caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin-converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure-volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6-fold, RV: 6.7-fold), and reduced load-independent systolic function (PRSW, LV: -54%, RV: -51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO-induced HF is not responsive to PDE5i therapy.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1172Subventions
Organisme : Grant Agency of Charles University (GAUK)
ID : 304121
Organisme : Ministry of Health of the Czech Republic
ID : NU20-02-00052
Organisme : Ministry of Health of the Czech Republic
ID : NU22-02-00161
Organisme : Project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES), funded by the European Union-Next Generation EU
ID : LX22NPO5104
Informations de copyright
© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
Références
Abassi Z, Goltsman I, Karram T, Winaver J, Hoffman A. Aortocaval fistula in rat: a unique model of volume-overload congestive heart failure and cardiac hypertrophy. J Biomed Biotechnol. 2011;2011:e729497.
Benes J, Kazdova L, Drahota Z, et al. Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats. Clin Sci. 2011;121(1):29-41.
Melenovsky V, Benes J, Skaroupkova P, et al. Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats. Mol Cell Biochem. 2011;354(1):83-96.
Melenovsky V, Skaroupkova P, Benes J, Torresova V, Kopkan L, Cervenka L. The course of heart failure development and mortality in rats with volume overload due to aorto-caval fistula. Kidney Blood Press Res. 2012;35(3):167-173.
Havlenova T, Skaroupkova P, Miklovic M, et al. Right versus left ventricular remodeling in heart failure due to chronic volume overload. Sci Rep. 2021;11(1):1-17.
Miklovic M, Kala P, Melenovsky V. Simultaneous biventricular pressure-volume analysis in rats. J Physiol Pharmacol. 2023;74(2):131-147.
Dunkerly-Eyring B, Kass DA. Myocardial phosphodiesterases and their role in cGMP regulation. J Cardiovasc Pharmacol. 2020;75(6):483-493.
Nagendran J, Archer SL, Soliman D, et al. Phosphodiesterase type 5 is highly expressed in the hypertrophied human right ventricle, and acute inhibition of phosphodiesterase type 5 improves contractility. Circulation. 2007;116(3):238-248.
Pokreisz P, Vandenwijngaert S, Bito V, et al. Ventricular phosphodiesterase-5 expression is increased in patients with advanced heart failure and contributes to adverse ventricular remodeling after myocardial infarction in mice. Circulation. 2009;119(3):408-416.
Lu Z, Xu X, Hu X, et al. Oxidative stress regulates left ventricular PDE5 expression in the failing heart. Circulation. 2010;121(13):1474-1483.
Kishimoto I, Rossi K, Garbers DL. A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. Proc Natl Acad Sci U S A. 2001;98(5):2703-2706.
Das A, Xi L, Kukreja RC. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem. 2005;280(13):12944-12955.
Takimoto E, Champion HC, Li M, et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med. 2005;11(2):214-222.
Borgdorff MAJ, Bartelds B, Dickinson MG, et al. Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure-loaded right ventricle. Eur J Heart Fail. 2012;14(9):1067-1074.
Borgdorff MA, Bartelds B, Dickinson MG, et al. Sildenafil treatment in established right ventricular dysfunction improves diastolic function and attenuates interstitial fibrosis independent from afterload. Am J Physiol Heart Circ Physiol. 2014;307(3):H361-H369.
Schäfer S, Ellinghaus P, Janssen W, et al. Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling. Cardiovasc Res. 2009;82(1):30-39.
Toischer K, Rokita AG, Unsöld B, et al. Differential cardiac remodeling in preload versus afterload. Circulation. 2010;122(10):993-1003.
Dai W, Kloner RA, Dai W, Kloner RA. Is inhibition of phosphodiesterase type 5 by sildenafil a promising therapy for volume-overload heart failure? Circulation. 2012;125:1341-1343.
Friedberg MK, Redington AN. Right versus left ventricular failure: differences, similarities, and interactions. Circulation. 2014;129(9):1033-1044.
Forfia PR, Lee M, Tunin RS, Mahmud M, Champion HC, Kass DA. Acute phosphodiesterase 5 inhibition mimics hemodynamic effects of B-type natriuretic peptide and potentiates B-type natriuretic peptide effects in failing but not Normal canine heart. J Am Coll Cardiol. 2007;49(10):1079-1088.
Ghali-Ghoul R, Tahseldar-Roumieh R, Sabra R. Effect of chronic administration of sildenafil on sodium retention and on the hemodynamic complications associated with liver cirrhosis in the rat. Eur J Pharmacol. 2007;572(1):49-56.
Melenovsky V, Cervenka L, Viklicky O, et al. Kidney response to heart failure: proteomic analysis of cardiorenal syndrome. Kidney Blood Press Res. 2018;43(5):1437-1450.
Asakura M, Kitakaze M. Global gene expression profiling in the failing myocardium. Circ J. 2009;73(9):1568-1576.
Drake JI, Bogaard HJ, Mizuno S, et al. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol. 2011;45(6):1239-1247.
Kong Q, Blanton RM. Protein kinase G I and heart failure: shifting focus from vascular unloading to direct myocardial antiremodeling effects. Circ Heart Fail. 2013;6(6):1268-1283.
Takimoto E. Cyclic GMP-dependent signaling in cardiac myocytes. Circ J. 2012;76(8):1819-1825.
Weinberg EO, Schoen FJ, George D, et al. Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis. Circulation. 1994;90(3):1410-1422.
Lapointe N, Blais C, Adam A, et al. Comparison of the effects of an angiotensin-converting enzyme inhibitor and a vasopeptidase inhibitor after myocardial infarction in the rat. J Am Coll Cardiol. 2002;39(10):1692-1698.
Červenka L, Melenovský V, Husková Z, Škaroupková P, Nishiyama A, Sadowski J. Inhibition of soluble epoxide hydrolase counteracts the development of renal dysfunction and progression of congestive heart failure in Ren-2 transgenic hypertensive rats with aorto-caval fistula. Clin Exp Pharmacol Physiol. 2015;42(7):795-807.
Lange PE, Seiffert PA, Pries F, et al. Value of image enhancement and injection of contrast medium for right ventricular volume determination by two-dimensional echocardiography in congenital heart disease. Am J Cardiol. 1985;55(1):152-157.
Abraham D, Mao L. Cardiac pressure-volume loop analysis using conductance catheters in mice. J Vis Exp. 2015;2015(103):1-10.
Huber W, Carey VJ, Gentleman R, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115-121.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402-408.
McCall MN, McMurray HR, Land H, Almudevar A. On non-detects in qPCR data. Bioinformatics. 2014;30(16):2310-2316.
Sporková A, Kopkan L, Varcabová S, et al. Role of cytochrome P-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1468-R1475.
Harding SD, Sharman JL, Faccenda E, et al. The IUPHAR/BPS guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY. Nucleic Acids Res. 2018;46(D1):D1091-D1106.
Alexander SPH, Fabbro D, Kelly E, et al. THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: catalytic receptors. Br J Pharmacol. 2021;178(S1):S264-S312.
Petrak J, Pospisilova J, Sedinova M, et al. Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets-monoamine oxidase a and transglutaminase 2. Proteome Sci. 2011;9(1):69.
Kim KH, Kim YJ, Ohn JH, et al. Long-term effects of sildenafil in a rat model of chronic mitral regurgitation: benefits of ventricular remodeling and exercise capacity. Circulation. 2012;125(11):1390-1401.
Eskesen K, Olsen NT, Dimaano VL, et al. Sildenafil treatment attenuates ventricular remodeling in an experimental model of aortic regurgitation. SpringerPlus. 2015;4(1):592.
Castro LRV, Verde I, Cooper DMF, Fischmeister R. Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes. Circulation. 2006;113(18):2221-2228.
Lee DI, Zhu G, Sasaki T, et al. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature. 2015;519(7544):472-476.
Margulies KB, Burnett JC. Inhibition of cyclic GMP phosphodiesterases augments renal responses to atrial natriuretic factor in congestive heart failure. J Card Fail. 1994;1(1):71-80.
Charloux A, Piquard F, Doutreleau S, Brandenberger G, Geny B. Mechanisms of renal hyporesponsiveness to ANP in heart failure. Eur J Clin Invest. 2003;33(9):769-778.
Yamamoto T, Wada A, Ohnishi M, et al. Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal production of endothelin-1 in dogs with congestive heart failure. Clin Sci Lond Engl. 2002;103(suppl 48):258S-262S.
Chen HH, Huntley BK, Schirger JA, Cataliotti A, Burnett JC. Maximizing the renal cyclic 3′-5′-guanosine monophosphate system with type V phosphodiesterase inhibition and exogenous natriuretic peptide: a novel strategy to improve renal function in experimental overt heart failure. J Am Soc Nephrol. 2006;17(10):2742-2747.
Scott NJA, Rademaker MT, Charles CJ, Espiner EA, Richards AM. Hemodynamic, hormonal, and renal actions of phosphodiesterase-9 inhibition in experimental heart failure. J Am Coll Cardiol. 2019;74(7):889-901.
Lewis GD, Lachmann J, Camuso J, et al. Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure. Circulation. 2007;115(1):59-66.
Barnes H, Brown Z, Burns A, Williams T. Phosphodiesterase 5 inhibitors for pulmonary hypertension. Cochrane Database Syst Rev. 2019;1(1):1-131.
Melenovsky V, Kotrc M, Borlaug BA, et al. Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. J Am Coll Cardiol. 2013;62(18):1660-1670.
Kala P, Sedláková L, Škaroupková P, et al. Effect of angiotensin-converting enzyme blockade, alone or combined with blockade of soluble epoxide hydrolase, on the course of congestive heart failure and occurrence of renal dysfunction in Ren-2 transgenic hypertensive rats with aorto-caval fistula. Physiol Res. 2018;67(3):401-415.
Kratky V, Vanourkova Z, Sykora M, et al. AT1 receptor blocker, but not an ACE inhibitor, prevents kidneys from hypoperfusion during congestive heart failure in normotensive and hypertensive rats. Sci Rep. 2021;11(1):4271.
Jarkovská D, Miklovič M, Švíglerová J, et al. Effects of Trandolapril on structural, contractile and electrophysiological remodeling in experimental volume overload heart failure. Front Pharmacol. 2021;12:1-13.
Červenka L, Škaroupková P, Kompanowska-Jezierska E, Sadowski J. Sex-linked differences in the course of chronic kidney disease and congestive heart failure: a study in 5/6 nephrectomized Ren-2 transgenic hypertensive rats with volume overload induced using aorto-caval fistula. Clin Exp Pharmacol Physiol. 2016;43(10):883-895.