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Bradykinin (B2 independent effect of captopril on the development of pressure overload cardiac hypertrophy

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Abstract

Besides the reduction of angiotensin II formation, locally increased kinins may play a role in the cardiovascular action of angiotensin converting enzyme (ACE) inhibitors.

To characterize the contribution of bradykinin to the effects of ACE inhibition by captopril on the development of pressure overload hypertrophy, sham-operated rats and rats with ascending aortic constriction were treated with captopril (80 mg/kg/day) or captopril and B2-kinin receptor antagonist HOE 140 (0.5 mg/kg/day) for 7 weeks. Left ventricular mass and geometry, hydroxyproline concentration and myosin isozymes (marker of a fetal phenotype) were assessed. Rats with aortic constriction exhibited a marked increase in left ventricular weight and diastolic pressure-volume relationship was shifted to smaller volumes. Signs of congestive heart failure were not apparent. The hydroxyproline concentration remained unaltered. However, the proportion of isomyosin V3 was increased (p < 0.05). Administration of captopril reduced (p < 0.05) systolic blood pressure, body and cardiac weight in all treated rats. The reduction of left ventricular weight was disproportionally higher in pressure overloaded rats, thus the relative left ventricular weight decreased by 15% (p < 0.05). Captopril augmented the isomyosin V1 expression (p < 0.05) in sham operated as well as pressure overloaded rats. The isomyosin V1 percentage was inversely related to the relative left ventricular weight. Two different (p < 0.05) correlation lines were detected for untreated and captopril treated rats. None of captopril associated effects were removed by simultaneously administered B2 kinin receptor antagonist HOE 140.

Thus, stimulation of bradykinin B2 receptor appears not to mediate the effects of captopril on cardiac growth and contractile proteins during the development of pressure overload hypertrophy.

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References

  1. Linz W, Schö lkens BA, Ganten D: Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens A11: 1325–1350, 1989

    Google Scholar 

  2. Peeler TC, Baker KM, Esmurdoc CF, Chernin MI: Angiotensin converting enzyme inhibition in Dahl salt-sensitive rats. Mol Cell Biochem 104: 45–50, 1991

    Google Scholar 

  3. Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, Drexler H: Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation 89: 2273–2282, 1994

    Google Scholar 

  4. Turcani M, Rupp H: Development of pressure overload induced cardiac hypertrophy is unaffected by long-term treatment with losartan. Mol Cell Biochem 188: 225–233, 1998

    Google Scholar 

  5. Harada K, Komuro I, Shiojima I, Hayashi D, Kudoh S, Mizuno T, Kijima K, Matsubara H, Sugaya T, Murakami K, Yazaki Y: Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice. Circulation 97: 1952–1959, 1998

    Google Scholar 

  6. Linz W, Wiemer G, Gohlke P, Unger T, Schö lkens BA: Contribution of kinins to the cardiovascular actions of angioternsin-converting enzyme inhibitors. Pharmacol Rev 47: 25–49, 1995

    Google Scholar 

  7. Wirth K, Breipohl G, Stechl J, Knolle J, Henke S, Schö lkens B: DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (desArg10-[Hoe140]) is a potent bradykinin B1 receptor antagonist. Eur J Pharmacol 205: 217–218, 1991

    Google Scholar 

  8. Weinberg EO, Schoen FJ, George D, Kagaya Y, Douglas PS, Litwin SE, Schunkert H, Benedict CR, Lorell BH: 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 90: 1410–1422, 1994

    Google Scholar 

  9. Zarain-Herzberg A, Rupp H: Transcriptional modulators targeted at fuel metabolism of hypertrophied heart. Am J Cardiol 83: 31H–37H, 1999

    Google Scholar 

  10. Bao G, Gohlke P, Qadri F, Unger T: Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril. Hypertension 20: 74–79, 1992

    Google Scholar 

  11. Rupp H, Wahl R, Hansen M: Influence of diet and carnitine palmitoyltransferase 1 inhibition on myosin and sarcoplasmic reticulum. J Appl Physiol 72: 352–360, 1992

    Google Scholar 

  12. Stegemann H, Stalder K: Determination of hydroxyproline. Clin Chim Acta 18: 267–273, 1967

    Google Scholar 

  13. Pfeffer MA, Braunwald E: Ventricular remodeling after myocardial infarction: Experimental observations and clinical implications. Circulation 81: 1161–1172, 1990

    Google Scholar 

  14. Linz W, Schö lkens BA, Ganten D: Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens 11: 1325–1350, 1989

    Google Scholar 

  15. Baker KM, Chernin MI, Wixson SK, Aceto JF: Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. Am J Physiol 259: H324–H332, 1990

    Google Scholar 

  16. Freslon JL, Giudicelli JF: Compared myocardial and vascular effects of captopril and dihydralazine during hypertension development in spontaneously hypertensive rats. Br J Pharmacol 80: 533–543, 1983

    Google Scholar 

  17. Linz W, Jessen T, Becker RHA, Schö lkens BA, Wiemer G: Long-term ACE inhibition doubles lifespan of hypertensive rats. Circulation 96: 3164–3172, 1997

    Google Scholar 

  18. Zierhut W, Zimmer HG, Gerdes AM: Effect of angiotensin converting enzyme inhibition on pressure-induced left ventricular hypertrophy in rats. Circ Res 69: 609–617, 1991

    Google Scholar 

  19. Litwin SE, Katz SE, Weinberg EO, Lorell BH, Aurigemma GP, Douglas PS: Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy. Chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure. Circulation 91: 2642–2654, 1995

    Google Scholar 

  20. Anning PB, Grocott-Mason RM, Lewis MJ, Shah AM: Enhancement of left ventricular relaxation in the isolated heart by an angiotensinconverting enzyme inhibitor. Circulation 92: 2660–2665, 1995

    Google Scholar 

  21. Raya TE, Gay G, Aguirre M, Goldman S: The importance of venodilatation in the prevention of left ventricular dilatation after chronic large myocardial infarction in rats: A comparison of captopril and hydralazin. Circ Res 64: 330–337, 1989

    Google Scholar 

  22. Mohabir R, Young SD, Strosberg AM: Role of angiotensin in pressure overload-induced hypertrophy in rats: Effects of angiotensin-converting enzyme inhibitors, an AT1 receptor antagonist, and surgical reversal. J Cardiovasc Pharmacol 23: 291–299, 1994

    Google Scholar 

  23. Ishygai Y, Mori T, Ikeda T, Fukuzawa A, Shibano T: Role of bradykinin-NO pathway in prevention of cardiac hypertrophy by ACE inhibitor in rat cardiomyocytes. Am J Physiol 273: H2659–H2663, 1997

    Google Scholar 

  24. Ritchie RH, Marsh JD, Lancaster WD, Diglio CA, Schiebinger RJ: Bradykinin blocks angiotensin II-induced hypertrophy in the presence of endothelial cells. Hypertension 31(part 1): 39–44, 1998

    Google Scholar 

  25. Shirotani P, Yui Y, Hattori R, Kawai C: U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells. Prostaglandins 41: 97–110, 1991

    Google Scholar 

  26. Rö sen P, Eckel J, Reinauer H: Influence of bradykinin on glucose uptake and metabolism studied in isolated cardiac myocytes and isolated perfused rat hearts. Hoppe Seyler Z Physiol Chem 364: 1431–1438, 1983

    Google Scholar 

  27. Henriksen EJ, Jacob S, Kinnick TR, Youngblood EB, Schmit MB, Dietze GJ: ACE inhibition and glucose transport in insulin-resistant muscle: Roles of bradykinin and nitric oxide. Am J Physiol 277: R332–R36, 1999

    Google Scholar 

  28. Cachofeiro V, Maeso R, Rodrigo E, Navarro J, Ruilope LM, Lahera V: Nitric oxide and prostaglandins in the prolonged effects of losartan and ramipril in hypertension. Hypertension 26: 236–243, 1995

    Google Scholar 

  29. Ota Y, Kugiyama K, Sugiyama S, Ohgushi M, Matsumura T, Doi H, Ogata N, Oka H, Yasue H: Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract–role of free radicals and attenuation by captopril. Atherosclerosis 131: 195–202, 1997

    Google Scholar 

  30. Ruiz FJ, Salom MG, Ingles AC, Quesada T, Vicente E, Carbonell LF: N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am J Physiol 267: R767–R772, 1994

    Google Scholar 

  31. Van Gilst VM, Wijingarden JV, Scholtens E, deGraeff PA, deLangen CDJ, Wesseling H: Captopril induced increase in coronary flow: An SHdependent effect on arachidonic metabolism. J Cardiovasc Pharmacol 9(suppl 2): S31–S36, 1987

    Google Scholar 

  32. Moroi M, Akatsuka N, Fukazawa M, Hara K, Ishikawa M, Aikawa J, Namiki A, Yamaguchi T: Endothelium-dependent relaxation by angiotensin-converting enzyme inhibitors in canine femoral arteries. Am J Physiol 266: H583–H589, 1994

    Google Scholar 

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Authors and Affiliations

  1. Institute of Pathophysiology, Medical School, Comenius University, Slovak Republic

    Marian Turcani

  2. Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology, Philipps University of Marburg, Marburg, Germany

    Heinz Rupp

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  1. Marian Turcani
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  2. Heinz Rupp
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Turcani, M., Rupp, H. Bradykinin (B2 independent effect of captopril on the development of pressure overload cardiac hypertrophy. Mol Cell Biochem 212, 219–225 (2000). https://doi.org/10.1023/A:1007154315380

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