Chronic volume overload induces multiple cardiac remodeling processes that finally result in eccentric cardiac hypertrophy and heart failure. We have hypothesized that chronic angiotensin-converting enzyme (ACE) inhibition by trandolapril might affect various remodeling processes differentially, thus allowing their dissociation. Cardiac remodeling due to chronic volume overload and the effects of trandolapril were investigated in rats with an aortocaval fistula (ACF rats). The aortocaval shunt was created using a needle technique and progression of cardiac remodeling to heart failure was followed for 24 weeks. In ACF rats, pronounced eccentric cardiac hypertrophy and contractile and proarrhythmic electrical remodeling were associated with increased mortality. Trandolapril substantially reduced the electrical proarrhythmic remodeling and mortality, whereas the effect on cardiac hypertrophy was less pronounced and significant eccentric hypertrophy was preserved. Effective suppression of electrical proarrhythmic remodeling and mortality but not hypertrophy indicates that the beneficial therapeutic effects of ACE inhibitor trandolapril in volume overload heart failure might be dissociated from pure antihypertrophic effects.

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czechia

Center for Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czechia

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czechia

Department of Pathophysiology 2 Faculty of Medicine Charles University Prague Czechia

Department of Physiology Faculty of Medicine in Pilsen Charles University Pilsen Czechia

Zobrazit více v PubMed

Abassi Z., Goltsman I., Karram T., Winaver J., Hoffman A., Abassi Z., et al. (2011). Aortocaval Fistula in Rat: a Unique Model of Volume-Overload Congestive Heart Failure and Cardiac Hypertrophy. J. Biomed. Biotechnol. 2011, 729497. 10.1155/2011/729497 PubMed DOI PMC

Alvin Z., Laurence G. G., Coleman B. R., Zhao A., Hajj-Moussa M., Haddad G. E. (2011a). Regulation of L-type Inward Calcium Channel Activity by Captopril and Angiotensin II via the Phosphatidyl Inositol 3-kinase Pathway in Cardiomyocytes from Volume-Overload Hypertrophied Rat Hearts. Can. J. Physiol. Pharmacol. 89, 206–215. 10.1139/Y11-011 PubMed DOI PMC

Alvin Z. V., Laurence G. G., Coleman B. R., Zhao A., Hajj-Moussa M., Haddad G. E. (2011b). Regulation of the Instantaneous Inward Rectifier and the Delayed Outward Rectifier Potassium Channels by Captopril and Angiotensin II via the Phosphoinositide-3 Kinase Pathway in Volume-Overload-Induced Hypertrophied Cardiac Myocytes. Med. Sci. Monit. 17, BR165–72. 10.12659/msm.881843 PubMed DOI PMC

Arsenault M., Zendaoui A., Roussel E., Drolet M. C., Dhahri W., Grenier A., et al. (2013). Angiotensin II-Converting Enzyme Inhibition Improves Survival, Ventricular Remodeling, and Myocardial Energetics in Experimental Aortic Regurgitation. Circ. Heart Fail. 6, 1021–1028. 10.1161/CIRCHEARTFAILURE.112.000045 PubMed DOI

Benes J., Melenovsky V., Skaroupkova P., Pospisilova J., Petrak J., Cervenka L., et al. (2011). Myocardial Morphological Characteristics and Proarrhythmic Substrate in the Rat Model of Heart Failure Due to Chronic Volume Overload. Anat. Rec. (Hoboken) 294, 102–111. 10.1002/ar.21280 PubMed DOI

Brower G. L., Henegar J. R., Janicki J. S. (1996). Temporal Evaluation of Left Ventricular Remodeling and Function in Rats with Chronic Volume Overload. Am. J. Physiol. 271, H2071–H2078. 10.1152/ajpheart.1996.271.5.H2071 PubMed DOI

Brower G. L., Janicki J. S. (2001). Contribution of Ventricular Remodeling to Pathogenesis of Heart Failure in Rats. Am. J. Physiol. Heart Circ. Physiol. 280, H674–H683. 10.1152/ajpheart.2001.280.2.H674 PubMed DOI

Brower G. L., Levick S. P., Janicki J. S. (2015). Differential Effects of Prevention and Reversal Treatment with Lisinopril on Left Ventricular Remodelling in a Rat Model of Heart Failure. Heart Lung Circ. 24, 919–924. 10.1016/j.hlc.2015.02.023 PubMed DOI PMC

Červenka L., Melenovský V., Husková Z., Škaroupková P., Nishiyama A., Sadowski J. (2015a). 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. 42, 795–807. 10.1111/1440-1681.12419 PubMed DOI

Červenka L., Melenovský V., Husková Z., Sporková A., Bürgelová M., Škaroupková P., et al. (2015b). Inhibition of Soluble Epoxide Hydrolase Does Not Improve the Course of Congestive Heart Failure and the Development of Renal Dysfunction in Rats with Volume Overload Induced by Aorto-Caval Fistula. Physiol. Res. 64, 857–873. 10.33549/physiolres.932977 PubMed DOI PMC

Chaggar P. S., Malkin C. J., Shaw S. M., Williams S. G., Channer K. S. (2009). Neuroendocrine Effects on the Heart and Targets for Therapeutic Manipulation in Heart Failure. Cardiovasc. Ther. 27, 187–193. 10.1111/j.1755-5922.2009.00094.x PubMed DOI

Chevalier B., Heudes D., Heymes C., Basset A., Dakhli T., Bansard Y., et al. (1995). Trandolapril Decreases Prevalence of Ventricular Ectopic Activity in Middle-Aged SHR. Circulation 92, 1947–1953. 10.1161/01.cir.92.7.1947 PubMed DOI

Cutler M. J., Jeyaraj D., Rosenbaum D. S. (2011). Cardiac Electrical Remodeling in Health and Disease. Trends Pharmacol. Sci. 32, 174–180. 10.1016/j.tips.2010.12.001 PubMed DOI PMC

Dell'italia L. J., Balcells E., Meng Q. C., Su X., Schultz D., Bishop S. P., et al. (1997). Volume-overload Cardiac Hypertrophy Is Unaffected by ACE Inhibitor Treatment in Dogs. Am. J. Physiol. 273, H961–H970. 10.1152/ajpheart.1997.273.2.H961 PubMed DOI

Diaz A., Ducharme A. (2008). Update on the Use of Trandolapril in the Management of Cardiovascular Disorders. Vasc. Health Risk Manag. 4, 1147–1158. 10.2147/vhrm.s3467 PubMed DOI PMC

Ding Y. F., Brower G. L., Zhong Q., Murray D., Holland M., Janicki J. S., et al. (2008). Defective Intracellular Ca2+ Homeostasis Contributes to Myocyte Dysfunction During Ventricular Remodelling Induced by Chronic Volume Overload in Rats. Clin. Exp. Pharmacol. Physiol. 35, 827–835. 10.1111/j.1440-1681.2008.04923.x PubMed DOI

Essayagh B., Sabbag A., Antoine C., Benfari G., Yang L. T., Maalouf J., et al. (2020). Presentation and Outcome of Arrhythmic Mitral Valve Prolapse. J. Am. Coll. Cardiol. 76, 637–649. 10.1016/j.jacc.2020.06.029 PubMed DOI

Flaim S. F., Minteer W. J., Nellis S. H., Clark D. P. (1979). Chronic Arteriovenous Shunt: Evaluation of a Model for Heart Failure in Rat. Am. J. Physiol. 236, H698–H704. 10.1152/ajpheart.1979.236.5.H698 PubMed DOI

Fornes P., Richer C., Pussard E., Heudes D., Domergue V., Giudicelli J. F. (1992). Beneficial Effects of Trandolapril on Experimentally Induced Congestive Heart Failure in Rats. Am. J. Cardiol. 70, 43D–51D. 10.1016/0002-9149(92)90271-y PubMed DOI

Garcia R., Diebold S. (1990). Simple, Rapid, and Effective Method of Producing Aortocaval Shunts in the Rat. Cardiovasc. Res. 24, 430–432. 10.1093/cvr/24.5.430 PubMed DOI

Gardner J. D., Brower G. L., Janicki J. S. (2002). Gender Differences in Cardiac Remodeling Secondary to Chronic Volume Overload. J. Card. Fail. 8, 101–107. 10.1054/jcaf.2002.32195 PubMed DOI

Gilat E., Girouard S. D., Pastore J. M., Laurita K. R., Rosenbaum D. S. (1998). Angiotensin-converting Enzyme Inhibition Produces Electrophysiologic but Not Antiarrhythmic Effects in the Intact Heart. J. Cardiovasc. Pharmacol. 31, 734–740. 10.1097/00005344-199805000-00012 PubMed DOI

Guggilam A., Hutchinson K. R., West T. A., Kelly A. P., Galantowicz M. L., Davidoff A. J., et al. (2013). In Vivo and In Vitro Cardiac Responses to Beta-Adrenergic Stimulation in Volume-Overload Heart Failure. J. Mol. Cel Cardiol 57, 47–58. 10.1016/j.yjmcc.2012.11.013 PubMed DOI PMC

Hammond H. K., Roth D. A., Insel P. A., Ford C. E., White F. C., Maisel A. S., et al. (1992). Myocardial Beta-Adrenergic Receptor Expression and Signal Transduction after Chronic Volume-Overload Hypertrophy and Circulatory Congestion. Circulation 85, 269–280. 10.1161/01.CIR.85.1.269 PubMed DOI

Harris G. S., Lust R. M., Katwa L. C. (2007). Hemodynamic Effects of Chronic Urotensin II Administration in Animals with and without Aorto-Caval Fistula. Peptides 28, 1483–1489. 10.1016/j.peptides.2007.04.018 PubMed DOI PMC

Hatt P. Y., Rakusan K., Gastineau P., Laplace M., Cluzeaud F. (1980). Aorto-caval Fistula in the Rat. An Experimental Model of Heart Volume Overloading. Basic Res. Cardiol. 75, 105–108. 10.1007/BF02001401 PubMed DOI

Hatt P. Y., Rakusan K., Gastineau P., Laplace M. (1979). Morphometry and Ultrastructure of Heart Hypertrophy Induced by Chronic Volume Overload (Aorto-caval Fistula in the Rat). J. Mol. Cel Cardiol 11, 989–998. 10.1016/0022-2828(79)90390-0 PubMed DOI

Hill J. A. (2003). Electrical Remodeling in Cardiac Hypertrophy. Trends Cardiovasc. Med. 13, 316–322. 10.1016/j.tcm.2003.08.002 PubMed DOI

Hutchinson K. R., Guggilam A., Cismowski M. J., Galantowicz M. L., West T. A., Stewart J. A., Jr., et al. (2011). Temporal Pattern of Left Ventricular Structural and Functional Remodeling Following Reversal of Volume Overload Heart Failure. J. Appl. Physiol. 111 (6), 1778–1788. 10.1152/japplphysiol.00691.2011 PubMed DOI PMC

Ichihara A., Hayashi M., Koura Y., Tada Y., Hirota N., Saruta T. (2003). Long-term Effects of Intensive Blood-Pressure Lowering on Arterial wall Stiffness in Hypertensive Patients. Am. J. Hypertens. 16, 959–965. 10.1016/s0895-7061(03)01004-5 PubMed DOI

Kehat I., Molkentin J. D. (2010). Molecular Pathways Underlying Cardiac Remodeling during Pathophysiological Stimulation. Circulation 122, 2727–2735. 10.1161/CIRCULATIONAHA.110.942268 PubMed DOI PMC

Kemp C. D., Conte J. V. (2012). The Pathophysiology of Heart Failure. Cardiovasc. Pathol. 21, 365–371. 10.1016/j.carpath.2011.11.007 PubMed DOI

Kim H. N., Januzzi J. L. (2011). Natriuretic Peptide Testing in Heart Failure. Circulation 123, 2015–2019. 10.1161/CIRCULATIONAHA.110.9795009 PubMed DOI

Kmecova J., Klimas J. (2010). Heart Rate Correction of the QT Duration in Rats. Eur. J. Pharmacol. 641, 187–192. 10.1016/j.ejphar.2010.05.038 PubMed DOI

Koffi I., Lacolley P., Kirchengaast M., Pomiès J. P., Laurent S., Benetos A. (1998). Prevention of Arterial Structural Alterations with Verapamil and Trandolapril and Consequences for Mechanical Properties in Spontaneously Hypertensive Rats. Eur. J. Pharmacol. 361, 51–60. 10.1016/s0014-2999(98)00691-8 PubMed DOI

Kristen A. V., Kreusser M. M., Lehmann L., Kinscherf R., Katus H. A., Haass M., et al. (2006). Preserved Norepinephrine Reuptake but Reduced Sympathetic Nerve Endings in Hypertrophic Volume-Overloaded Rat Hearts. J. Card. Fail. 12, 577–583. 10.1016/j.cardfail.2006.05.006 PubMed DOI

Lee C. S., Tkacs N. C. (2008). Current Concepts of Neurohormonal Activation in Heart Failure: Mediators and Mechanisms. AACN Adv. Crit. Care 19, 364–367. 10.1097/01.AACN.0000340718.93742.c4 PubMed DOI

Liu Z., Hilbelink D. R., Crockett W. B., Gerdes A. M. (1991a). Regional Changes in Hemodynamics and Cardiac Myocyte Size in Rats with Aortocaval Fistulas. 1. Developing and Established Hypertrophy. Circ. Res. 69, 52–58. 10.1161/01.res.69.1.52 PubMed DOI

Liu Z., Hilbelink D. R., Gerdes A. M. (1991b). Regional Changes in Hemodynamics and Cardiac Myocyte Size in Rats with Aortocaval Fistulas. 2. Long-Term Effects. Circ. Res. 69, 59–65. 10.1161/01.res.69.1.59 PubMed DOI

Lloyd-Jones D. M., Larson M. G., Leip E. P., Beiser A., D'Agostino R. B., Kannel W. B., et al. (2002). Lifetime Risk for Developing Congestive Heart Failure: the Framingham Heart Study. Circulation 106, 3068–3072. 10.1161/01.cir.0000039105.49749.6f PubMed DOI

Lou Q., Janardhan A., Efimov I. R. (2012). Remodeling of Calcium Handling in Human Heart Failure. Adv. Exp. Med. Biol. 740, 1145–1174. 10.1007/978-94-007-2888-2_52 PubMed DOI PMC

Luo M., Anderson M. E. (2013). Mechanisms of Altered Ca²⁺ Handling in Heart Failure. Circ. Res. 113, 690–708. 10.1161/CIRCRESAHA.113.301651 PubMed DOI PMC

Mahajerin A., Gurm H. S., Tsai T. T., Chan P. S., Nallamothu B. K. (2007). Vasodilator Therapy in Patients with Aortic Insufficiency: a Systematic Review. Am. Heart J. 153, 454–461. 10.1016/j.ahj.2007.01.006 PubMed DOI

Meani P., Maloberti A., Sormani P., Colombo G., Giupponi L., Stucchi M., et al. (2018). Determinants of Carotid-Femoral Pulse Wave Velocity Progression in Hypertensive Patients over a 3.7 Years Follow-Up. Blood Press. 27, 32–40. 10.1080/08037051.2017.1378069 PubMed DOI

Melenovsky V., Cervenka L., Viklicky O., Franekova J., Havlenova T., Behounek M., et al. (2018). Kidney Response to Heart Failure: Proteomic Analysis of Cardiorenal Syndrome. Kidney Blood Press. Res. 43, 1437–1450. 10.1159/000493657 PubMed DOI

Melenovsky V., Skaroupkova P., Benes J., Torresova V., Kopkan L., Cervenka L. (2012). The Course of Heart Failure Development and Mortality in Rats with Volume Overload Due to Aorto-Caval Fistula. Kidney Blood Press. Res. 35, 167–173. 10.1159/000331562 PubMed DOI

Modesti P. A., Vanni S., Bertolozzi I., Cecioni I., Lumachi C., Perna A. M., et al. (2004). Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload. Hypertension 43, 101–108. 10.1161/01.HYP.0000104720.76179.18 PubMed DOI

Oliver-Dussault C., Ascah A., Marcil M., Matas J., Picard S., Pibarot P., et al. (2010). Early Predictors of Cardiac Decompensation in Experimental Volume Overload. Mol. Cel Biochem 338, 271–282. 10.1007/s11010-009-0361-5 PubMed DOI

Orsborne C., Chaggar P. S., Shaw S. M., Williams S. G. (2017). The Renin-Angiotensin-Aldosterone System in Heart Failure for the Non-specialist: the Past, the Present and the Future. Postgrad. Med. J. 93, 29–37. 10.1136/postgradmedj-2016-134045 PubMed DOI

Perry G. J., Wei C. C., Hankes G. H., Dillon S. R., Rynders P., Mukherjee R., et al. (2002). Angiotensin II Receptor Blockade Does Not Improve Left Ventricular Function and Remodeling in Subacute Mitral Regurgitation in the Dog. J. Am. Coll. Cardiol. 39, 1374–1379. 10.1016/s0735-1097(02)01763-1 PubMed DOI

Petrak J., Pospisilova J., Sedinova M., Jedelsky P., Lorkova L., Vit O., et al. (2011). 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. 9, 69. 10.1186/1477-5956-9-69 PubMed DOI PMC

Pfeffer M. A., Braunwald E., Moyé L. A., Basta L., Brown E. J., Cuddy T. E., et al. (1992). Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction. Results of the Survival and Ventricular Enlargement Trial. The SAVE Investigators. N. Engl. J. Med. 327, 669–677. 10.1056/NEJM199209033271001 PubMed DOI

Rea M. E., Dunlap M. E. (2008). Renal Hemodynamics in Heart Failure: Implications for Treatment. Curr. Opin. Nephrol. Hypertens. 17, 87–92. 10.1097/MNH.0b013e3282f357da PubMed DOI

Ruzicka M., Keeley F. W., Leenen F. H. (1994). The Renin-Angiotensin System and Volume Overload-Induced Changes in Cardiac Collagen and Elastin. Circulation 90, 1989–1996. 10.1161/01.cir.90.4.1989 PubMed DOI

Ruzicka M., Skarda V., Leenen F. H. (1995). Effects of ACE Inhibitors on Circulating versus Cardiac Angiotensin II in Volume Overload-Induced Cardiac Hypertrophy in Rats. Circulation 92, 3568–3573. 10.1161/01.cir.92.12.3568 PubMed DOI

Ruzicka M., Yuan B., Harmsen E., Leenen F. H. (1993). The Renin-Angiotensin System and Volume Overload-Induced Cardiac Hypertrophy in Rats. Effects of Angiotensin Converting Enzyme Inhibitor versus Angiotensin II Receptor Blocker. Circulation 87, 921–930. 10.1161/01.cir.87.3.921 PubMed DOI

Ryan T. D., Rothstein E. C., Aban I., Tallaj J. A., Husain A., Lucchesi P. A., et al. (2007). Left Ventricular Eccentric Remodeling and Matrix Loss Are Mediated by Bradykinin and Precede Cardiomyocyte Elongation in Rats with Volume Overload. J. Am. Coll. Cardiol. 49, 811–821. 10.1016/j.jacc.2006.06.083 PubMed DOI

Savarese G., Lund L. H. (2017). Global Public Health Burden of Heart Failure. Card. Fail. Rev. 3, 7–11. 10.15420/cfr.2016:25:2 PubMed DOI PMC

Schirone L., Forte M., Palmerio S., Yee D., Nocella C., Angelini F., et al. (2017). A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling. Oxidative Med. Cell Longevity 2017, 1–16. 10.1155/2017/3920195 PubMed DOI PMC

Sedmera D., Neckar J., Benes J., Pospisilova J., Petrak J., Sedlacek K., et al. (2016). Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload. Front. Physiol. 7, 367. 10.3389/fphys.2016.00367 PubMed DOI PMC

St John Sutton M. M., Pfeffer M. A., Plappert T., Rouleau J. L., Moyé L. A., Dagenais G. R., et al. (1994). Quantitative Two-Dimensional Echocardiographic Measurements Are Major Predictors of Adverse Cardiovascular Events after Acute Myocardial Infarction. The Protective Effects of Captopril. Circulation 89, 68–75. 10.1161/01.cir.89.1.68 PubMed DOI

Stumpe K. O., Sölle H., Klein H., Krück F. (1973). Mechanism of Sodium and Water Retention in Rats with Experimental Heart Failure. Kidney Int. 4, 309–317. 10.1038/ki.1973.122 PubMed DOI

Tanonaka K., Toga W., Yoshida H., Furuhama K., Takeo S. (2001). Effect of Long-Term Treatment with Trandolapril on Hsp72 and Hsp73 Induction of the Failing Heart Following Myocardial Infarction. Br. J. Pharmacol. 134, 969–976. 10.1038/sj.bjp.0704323 PubMed DOI PMC

Toischer K., Rokita A. G., Unsöld B., Zhu W., Kararigas G., Sossalla S., et al. (2010). Differential Cardiac Remodeling in Preload versus Afterload. Circulation 122, 993–1003. 10.1161/CIRCULATIONAHA.110.943431 PubMed DOI PMC

Topouchian J., Asmar R., Sayegh F., Rudnicki A., Benetos A., Bacri A. M., et al. (1999). Changes in Arterial Structure and Function under Trandolapril-Verapamil Combination in Hypertension. Stroke 30, 1056–1064. 10.1161/01.str.30.5.1056 PubMed DOI

Triposkiadis F., Karayannis G., Giamouzis G., Skoularigis J., Louridas G., Butler J. (2009). The Sympathetic Nervous System in Heart Failure Physiology, Pathophysiology, and Clinical Implications. J. Am. Coll. Cardiol. 54, 1747–1762. 10.1016/j.jacc.2009.05.015 PubMed DOI

van der Ent M., Remme W. J., de Leeuw P. W., Bartels G. L. (1998). Renal Hemodynamic Effects in Patients with Moderate to Severe Heart Failure during Chronic Treatment with Trandolapril. Cardiovasc. Drugs Ther. 12, 395–403. 10.1023/a:1007729002821 PubMed DOI

Varró A., Baczkó I. (2011). Cardiac Ventricular Repolarization reserve: a Principle for Understanding Drug-Related Proarrhythmic Risk. Br. J. Pharmacol. 164, 14–36. 10.1111/j.1476-5381.2011.01367.x PubMed DOI PMC

Wang X., Zhuo X., Gao J., Liu H., Lin F., Ma A. (2019). Neuregulin-1beta Partially Improves Cardiac Function in Volume-Overload Heart Failure Through Regulation of Abnormal Calcium Handling. Front Pharmacol 10, 616–36. 10.3389/fphar.2019.00616 PubMed DOI PMC

Westerhof N., O'Rourke M. F. (1995). Haemodynamic Basis for the Development of Left Ventricular Failure in Systolic Hypertension and for its Logical Therapy. J. Hypertens. 13, 943–952. 10.1097/00004872-199509000-00002 PubMed DOI

Willenbrock R., Stauss H., Scheuermann M., Osterziel K. J., Unger T., Dietz R. (1997). Effect of Chronic Volume Overload on Baroreflex Control of Heart Rate and Sympathetic Nerve Activity. Am. J. Physiol. 273, H2580–H2585. 10.1152/ajpheart.1997.273.6.H2580 PubMed DOI

Zeltser I., Gaynor J. W., Petko M., Myung R. J., Birbach M., Waibel R., et al. (2005). The Roles of Chronic Pressure and Volume Overload States in Induction of Arrhythmias: an Animal Model of Physiologic Sequelae after Repair of Tetralogy of Fallot. J. Thorac. Cardiovasc. Surg. 130, 1542–1548. 10.1016/j.jtcvs.2005.08.034 PubMed DOI

Renal denervation improves cardiac function independently of afterload and restores myocardial norepinephrine levels in a rodent heart failure model

Modulation of left ventricular hypertrophy in spontaneously hypertensive rats by acetylcholinesterase and ACE inhibitors: physiological, biochemical, and proteomic studies

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

The treatment with trandolapril and losartan attenuates pressure and volume overload alternations of cardiac connexin-43 and extracellular matrix in Ren-2 transgenic rats

Regulation of Prepro-NeuropeptideW/B and Its Receptor in the Heart of ZDF Rats: An Animal Model of Type II DM