Evaluation of the renin-angiotensin system in cardiac tissues of cats with pressure-overload cardiac hypertrophy

Masami Uechi Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino 1866, Fujisawa, Kanagawa 252-8510, Japan.

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Yoshiyuki Tanaka Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino 1866, Fujisawa, Kanagawa 252-8510, Japan.

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Yoshitaka Aramaki Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.

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Yasutomo Hori Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.

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Yumi Ishikawa Veterinary Teaching Hospital, School of Veterinary Medicine and Animal Science, Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.

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Takashi Ebisawa Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino 1866, Fujisawa, Kanagawa 252-8510, Japan.

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Shigeki Yamano Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Kameino 1866, Fujisawa, Kanagawa 252-8510, Japan.

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Abstract

Objective—To clarify regulation of the renin-angiotensin (RA) system in cardiac tissues by measuring angiotensin-converting enzyme (ACE) and chymase activities in cats with pressure-overload cardiac hypertrophy.

Animals—13 adult cats.

Procedures—Pressure-overload cardiac hypertrophy was induced by coarctation of the base of the ascending aorta in 6 cats, and 7 cats served as untreated control animals. Cats were examined before and 3 months and 2 years after surgery. Two years after surgery, cardiac hypertrophy was confirmed by echocardiography, and the blood pressure gradient was measured at the site of constriction. Cats were euthanized, and ACE and chymase activities were measured in cardiac tissues.

Results—Mean ± SD pressure gradient across the aortic constriction was 63 ± 6 mm Hg. Chymase activity predominated (75% to 85%) in the RA system of the cardiac tissues of cats. Fibrosis in the wall of the left ventricle was detected in cats with hypertrophy, and fibrosis of the papillary muscle was particularly evident.

Conclusions and Clinical Relevance—Chronic pressure overload on the heart of cats can activate the RA system in cardiac tissues. A local increase in angiotensin II was one of the factors that sustained myocardial remodeling.

Abstract

Objective—To clarify regulation of the renin-angiotensin (RA) system in cardiac tissues by measuring angiotensin-converting enzyme (ACE) and chymase activities in cats with pressure-overload cardiac hypertrophy.

Animals—13 adult cats.

Procedures—Pressure-overload cardiac hypertrophy was induced by coarctation of the base of the ascending aorta in 6 cats, and 7 cats served as untreated control animals. Cats were examined before and 3 months and 2 years after surgery. Two years after surgery, cardiac hypertrophy was confirmed by echocardiography, and the blood pressure gradient was measured at the site of constriction. Cats were euthanized, and ACE and chymase activities were measured in cardiac tissues.

Results—Mean ± SD pressure gradient across the aortic constriction was 63 ± 6 mm Hg. Chymase activity predominated (75% to 85%) in the RA system of the cardiac tissues of cats. Fibrosis in the wall of the left ventricle was detected in cats with hypertrophy, and fibrosis of the papillary muscle was particularly evident.

Conclusions and Clinical Relevance—Chronic pressure overload on the heart of cats can activate the RA system in cardiac tissues. A local increase in angiotensin II was one of the factors that sustained myocardial remodeling.

Contributor Notes

Address correspondence to Dr. Uechi.
  • 1.

    Kramkowski K, Mogielnicki A, Buczko W. The physiological significance of the alternative pathways of angiotensin II production. J Physiol Pharmacol 2006;57:529539.

    • Search Google Scholar
    • Export Citation
  • 2.

    Lawson CR, Doulton TW, MacGregor GA. Autosomal dominant polycystic kidney disease: role of the renin-angiotensin system in raised blood pressure in progression of renal and cardiovascular disease. J Renin Angiotensin Aldosterone Syst 2006;7:139145.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol 2007;292:C82–C97.

    • Search Google Scholar
    • Export Citation
  • 4.

    Campese VM, Park J. The kidney and hypertension: over 70 years of research. J Nephrol 2006;19:691698.

  • 5.

    Lupu AN, Maxwel MH, Kaufman JJ, et al. Experimental unilateral renal artery constriction in the dog. Circ Res 1972;30:567574.

  • 6.

    Sadoshima J, Izumo S. Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Circ Res 1993;73:413423.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Shiota N, Fukamizu A, Takai S, et al. Activation angiotensin IIforming chymase in the cardiomyopathic hamster heart. J Hypertens 1997;15:431440.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Yamazaki T, Komuro I, Kudoh S, et al. Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy. Circ Res 1995;75:258265.

    • Search Google Scholar
    • Export Citation
  • 9.

    Hirsch AT, Duprez D. The potential role of angiotensin-converting enzyme inhibition in peripheral arterial disease. Vasc Med 2003;8:273278.

  • 10.

    Aksnes TA, Flaa A, Strand A, et al. Prevention of new-onset atrial fibrillation and its predictors with angiotensin II-receptor blockers in the treatment of hypertension and heart failure. J Hypertens 2007;25:1523.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Moesgaard SG, Pedersen LG, Teerlink T, et al. Neurohormonal and circulatory effects of short-term treatment with enalapril and quinapril in dogs with asymptomatic mitral regurgitation. J Vet Intern Med 2005;19:712719.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Atkins CE, Brown WA, Coats JR, et al. Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation. J Am Vet Med Assoc 2002;221:654658.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Rush JE, Freeman LM, Brown DJ, et al. The use of enalapril in the treatment of feline hypertrophic cardiomyopathy. J Am Anim Hosp Assoc 1998;34:3841.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Dell'Italia LJ, Balcells E, Meng QC, et al. Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs. Am J Physiol 1997;273:H961–H970.

    • Search Google Scholar
    • Export Citation
  • 15.

    Balcells E, Meng QC, Hageman GR, et al. Angiotensin II formation in dog heart is mediated by different pathways in vivo and in vitro. Am J Physiol 1996;40:H417–H421.

    • Search Google Scholar
    • Export Citation
  • 16.

    Takai S, Shiota N, Yamamoto D, et al. Purification and characterization of angiotensin II-generating chymase from hamster cheek pouch. Life Sci 1996;58:591597.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Nishimura H, Buikema H, Baltau O, et al. Functional evidence for alternative ANG II-forming pathways in hamster cardiovascular system. Am J Physiol 1998;275:H1307–H1312.

    • Search Google Scholar
    • Export Citation
  • 18.

    Urata H. Pathological involvement of chymase-dependent angiotensin II formation in the development of cardiovascular disease. J Renin Angiotensin Aldosterone Syst 2000;1:3537.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Doggrell SA, Wanstall JC. Cardiac chymase: pathophysiological role and therapeutic potential of chymase inhibitors. Can J Physiol Pharmacol 2005;83:123130.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Helske S, Lindstedt KA, Laine M, et al. Induction of local angiotensin II-producing systems in stenotic aortic valves. J Am Coll Cardiol 2004;44:18591866.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Urata H, Healy B, Stewart RW, et al. Angiotensin II-forming pathways in normal and failing human hearts. Circ Res 1990;66:883890.

  • 22.

    Takai S, Shiota N, Sakaguchi M, et al. Characterization of chymase from human vascular tissues. Clin Chim Acta 1997;265:1320.

  • 23.

    Akasu M, Urata H, Kinoshita A, et al. Differences in tissue angiotensin II-forming pathways by species and organs in vitro. Hypertension 1998;32:514520.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Balcells E, Meng QC, Johnson WH Jr, et al. Angiotensin II formation from ACE and chymase in human and animal hearts: methods and species considerations. Am J Physiol 1997;273: H1769–H1774.

    • Search Google Scholar
    • Export Citation
  • 25.

    Danser AH, Schalekamp MA, Bax WA, et al. Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995;92:13871388.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Dell'Italia LJ, Meng QC, Balcells E, et al. Increased ACE and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation. Am J Physiol 1995;269:H2065–H2073.

    • Search Google Scholar
    • Export Citation
  • 27.

    Ettinger SJ, Benitz AM, Ericsson GF, et al. Effects of enalapril maleate on survival of dogs with naturally acquired heart failure. J Am Vet Med Assoc 1998;213:15731577.

    • Search Google Scholar
    • Export Citation
  • 28.

    Aramaki Y, Uechi M, Takase K. Angiotensin converting enzyme and chymase activity in the feline heart and serum. J Vet Med Sci 2003;65:11151118.

  • 29.

    Lupu AN, Maxwel MH, Kaufman JJ. Mechanisms of hypertension during the chronic phase of the one-clip, two-kidney model in the dog. Circ Res 1977;40:I57–I61.

    • Search Google Scholar
    • Export Citation
  • 30.

    Maxwel MH, Lupu AN, Viskoper RJ, et al. Mechanisms of hypertension during the acute and intermediate phases of the oneclip, two-kidney model in the dog. Circ Res 1977;40:I24–I28.

    • Search Google Scholar
    • Export Citation
  • 31.

    Jin D, Takai S, Yamada M, et al. Possible role of cardiac chymase after myocardial infarction in hamster hearts. Jpn J Pharmacol 2001;86:203214.

  • 32.

    Carlos Sampedrano C, Chetboul V, Gouni V, et al. Systolic and diastolic myocardial dysfunction in cats with hypertrophic cardiomyopathy or systemic hypertension. J Vet Intern Med 2006;20:11061115.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    MacDonald KA, Kittleson MD, Larson RF, et al. The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure. J Vet Intern Med 2006;20:10931105.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Mizutani H, Koyama H, Watanabe T, et al. Evaluation of the clinical efficacy of benazepril in the treatment of chronic renal insufficiency in cats. J Vet Intern Med 2006;20:10741079.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35.

    King JN, Gunn-Moore DA, Tasker S, et al. Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med 2006;20:10541064.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Brown CA, Munday JS, Mathur S, et al. Hypertensive encephalopathy in cats with reduced renal function. Vet Pathol 2005;42:642649.

  • 37.

    Buranakarl C, Mathur S, Brown SA. Effects of dietary sodium chloride intake on renal function and blood pressure in cats with normal and reduced renal function. Am J Vet Res 2004;65:620627.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Brodsky S, Gurbanov K, Abassi Z, et al. Effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure. Hypertension 1998;32:746752.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Wagner C, de Wit C, Kurtz L, et al. Connexin40 is essential for the pressure control of renin synthesis and secretion. Circ Res 2007;100:556563.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

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

    • Search Google Scholar
    • Export Citation
  • 41.

    Ruzicka M, Yuan B, Harmsen E, et al. The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker. Circulation 1993;87:921930.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Shiota N, Jin D, Takai S, et al. Chymase is activated in the hamster heart following ventricular fibrosis during the chronic stage of hypertension. FEBS Lett 1997;406:301304.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Kai H, Mori T, Tokuda K, et al. Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II. Hypertens Res 2006;29:711718.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Kanemitsu H, Takai S, Tsuneyoshi H, et al. Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats. Hypertens Res 2006;29:5764.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45.

    Hoshino F, Urata H, Inoue Y, et al. Chymase inhibitor improves survival in hamsters with myocardial infarction. J Cardiovasc Pharmacol 2003;41(suppl 1):S11–S18.

    • Search Google Scholar
    • Export Citation
  • 46.

    Miyazaki M, Takai S, Jin D, et al. Pathological roles of angiotensin II produced by mast cell chymase and the effects of chymase inhibition in animal models. Pharmacol Ther 2006;112:668676.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Kanemitsu H, Takai S, Tsuneyoshi H, et al. Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats. Hypertens Res 2006;29:5764.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Yamamoto K, Mano T, Yoshida J, et al. ACE inhibitor and angiotensin II type 1 receptor blocker differently regulate ventricular fibrosis in hypertensive diastolic heart failure. J Hypertens 2005;23:393400.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49.

    Funabiki K, Onishi K, Dohi K, et al. Combined angiotensin receptor blocker and ACE inhibitor on myocardial fibrosis and left ventricular stiffness in dogs with heart failure. Am J Physiol Heart Circ Physiol 2004;287:H2487–H2492.

    • Search Google Scholar
    • Export Citation
  • 50.

    Taniguchi I, Kawai M, Date T, et al. Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy. Circ J 2006;70:9951000.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51.

    Kjeldsen SE, Strand A, Julius S, et al. Mechanism of angiotensin II type 1 receptor blocker action in the regression of left ventricular hypertrophy. J Clin Hypertens 2006;8:487492.

    • Crossref
    • Search Google Scholar
    • Export Citation

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