|
Sign In to gain access to subscriptions and/or personal tools.
|
Combined renin-angiotensin system blockade and dietary sodium restriction impairs cardiomyocyte contractility
Petcharat Trongtorsak
Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia
Trefor O Morgan
Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia
Lea MD Delbridge
Department of Physiology, University of Melbourne, Parkville, Victoria, 3010, Australia, Imd{at}unimelb.edu.au
Introduction Blockade of the renin-angiotensin system (RAS) by combined angiotensin-converting enzyme inhibitor and angiotensin type 1 receptor (AT1) antagonist treatment with reduced dietary sodium intake produces suppression of cardiac growth and regression of cardiac hypertrophy. The purpose of this study was to investigate whether cardiac growth suppression by combined RAS blockade under conditions of dietary sodium restriction is associated with cardiomyocyte atrophy and contractile dysfunction and whether this intervention modifies cardiomyocyte inotropic responsiveness to angiotensin II (Ang II).
Methods Rats were fed a high (4% w/w) or low (0.2% w/w) NaCl diet for six days. Both groups were then given a combined intraperitoneal injection of perindopril (6 mg/kg/day) and losartan (10 mg/kg/day) with maintained dietary treatment for another seven days. At the end of the treatment period, animals were anaesthetised and their hearts were removed and weighed. Left ventricular cardiomyocytes were isolated by enzymatic dissociation and cell dimensions were evaluated. A line scan camera and digital imaging technique were used to assess cardiomyocyte contraction and inotropic responses to exogenous Ang II (10-10 to 10-8 M).
Results Dietary treatment alone had no effect on body growth, whereas combined RAS blockade suppressed somatic growth in the low sodium (LS) group, compared with the high sodium (HS) group. This growth suppression in the LS group was also evident in the heart at the organ and cellular level. Studies of cardiomyocyte contraction showed that myocytes from the LS group exhibited contractile instability and depression of contractile performance. Compared with the HS group, myocytes from the LS group showed a significant reduction in maximum cell shortening (6.40±0.17 vs. 7.32±0.16% resting length, p<0.05), and maximum rate of shortening (3.85±0.14 vs. 4.29±0.11 cell length/ms, p<0.05). Myocytes of the HS group exhibited negative inotropic responses to Ang II at all concentrations tested, with a significant reduction in maximum cell shortening by 11—16% after 12 minutes peptide exposure (p<0.05 vs. non-treated control). In comparison, Ang II elicited both positive and negative responses in myocytes from the LS group, with a predominant negative inotropic effect.
Conclusions This study provides evidence that combined RAS blockade treatment under restricted sodium intake conditions can impair cardiomyocyte contractile function in association with cardiomyocyte growth suppression. Chronic RAS blockade qualitatively alters the intrinsic inotropic status and responsiveness of ventricular cardiomyocytes, and this shift is further modulated by dietary sodium intake conditions.
Key Words: angiotensin II • dietary sodium • angiotensin type 1 receptor antagonism • angiotensin-converting enzyme inhibition • cardiomyocyte contraction • inotropy
References
- Kim S., Iwao H. Molecular and cellular mechanism of angiotensin II-mediated cardiovascular and renal diseases. Pharmacol Rev 2000;52:11-34.[Abstract/Free Full Text]
- Lui Y-H.,Yang X-P., Sharo VG et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor antagonists in rats with heart failure. J Clin Invest 1997; 99:1926-35.[Web of Science][Medline]
[Order article via Infotrieve]
- Azizi M., Linhart A., Alexander J. et al. Pilot study of combined blockade of the renin-angiotensin system in essential hypertension patients. J Hypertens 2000;18:1139-47.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Kim S., Zhan Y., Izumi Y., Iwao H. Cardiovascular effects of combination of perindopril, candesartan, and amlodipine in hypertensive rats. Hypertension 2000;35:769-74.[Abstract/Free Full Text]
- Ohta T., Hasebe N., Tsuji S. et al. Effects of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor blocker on cardiac dysfunction induced by isoproterenol in dogs. J Cardiovasc Pharmacol 2001;38(suppl 1):S63-S67.[Web of Science][Medline]
[Order article via Infotrieve]
- Easthope SE, Jarvis B. Candesartan cilexetil: An update of its use in essential hypertension. Drugs 2002;62:1253-87.of[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- van den Meiracker AH, Man in't Veld AJ, Admiraal PJJ, Ritsema van Eck HJ, Boomsma F., Derkx FHM. Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response? J Hypertens 1992;10:803-12.[Web of Science][Medline]
[Order article via Infotrieve]
- Azizi M., Guyene T.-T, Chatellier G., Wargon M., Menard J. Additive effect of losartan and enalapril on blood pressure and plasma active renin. Hypertension 1997;29:634-40.[Abstract/Free Full Text]
- Menard J., Campbell DJ, Azizi M., Gonzales M-F. Synergistic effects of ACE inhibition and angiotensin II antagonism on blood pressure, cardiac weight, and renin in spontaneously hypertensive rats. Circulation 1997;96:3072-8.[Abstract/Free Full Text]
- Dostal DE, Baker KM The cardiac renin-angiotensin system: conceptual, or a regulator of cardiac function? Circ Res 1999;85:643-50.[Abstract/Free Full Text]
- Kawai H., Stevens SY, Liang CS Renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure. Am J Physiol 2000;279:H3012-H3019.[Web of Science]
- He FJ, Markandu ND, Sagnella GA, MacGregor GA Importance of the renin system in determining blood pressure fall with salt restriction in black and white hypertensives. Hypertension 1998;32:820-4.[Abstract/Free Full Text]
- Cholewa BC, Mattson DL Role of the renin-angiotensin system during alterations of sodium intake in conscious mice. Am J Physiol 2001;281:R987-R993.[Web of Science]
- Morgan TO, Aubert J.-F, Wang Q. Sodium, angiotensin II, blood pressure, and cardiac hypertrophy. Kidney Int 1998; 54(suppl 67):213-15.[CrossRef]
- Teravainen T-L., Mervaala EMA, Laakso J., Paakkari I., Vapaatalo H., Karppanen H. Influence of age on cardiovascular effects of increased dietary sodium and angiotensin-converting enzyme inhibition in normotensive Wistar rats. J Pharm Pharmacol 1997;49:912-18.[Web of Science][Medline]
[Order article via Infotrieve]
- Herlitz H., Dahlof B., Jonsson O., Friberg P. Relationship between salt and blood pressure in hypertensive patients on chronic ACE-inhibition. Blood Pressure 1998;7:47-52.[CrossRef][Medline]
[Order article via Infotrieve]
- Griffiths CD, Morgan TO, Belbridge LM Effects of combined administration of ACE inhibitor and angiotensin II receptor antagonist are prevented by a high NaCl intake. J Hypertens 2001;19:2087-95.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Abro E., Griffiths CD, Morgan TO, Delbridge LM Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction. JRAAS 2001;2:148-53.
- Delbridge LM, Morgan TO, Harris PJ Effects of endothelin-1 on the contractility of cardiomyocytes from the spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 1995; 22:755-62.[Web of Science][Medline]
[Order article via Infotrieve]
- Di Nicolantonio R., Silvapulle MJ, Spargo S., Morgan TO High salt diet decreases longevity in the spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 1988;15:357-9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Delbridge LM, Harris PJ, Morgan TO Characterization of single heart cells contractility by rapid imaging. Clin Exp Pharmacol Physiol 1989;16:179-84.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Delbridge LM, Harris PJ, Pringle JT, Dally LJ, Morgan TO A superfusion bath for single-cell recording with high-precision optical depth control, temperature regulation, and rapid solution switching. Eur J Physiol 1990;416:94-7.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Harris PJ, Stewart D., Cullinan MC, Delbridge LM, Dally L., Grinwald P. Rapid measurement of isolated cardiac muscle cell length using a line-scan camera. IEEE Trans Biomed Eng 1987;34:463-7[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Navis G., de Jong PE, Donker AJM, van der Hem K., de Zeeuw D. Diuretic effects of angiotensin-converting enzyme inhibition: comparison of low and liberal sodium diet in hypertensive patients. J Cardiovasc Pharmacol 1987;9:743-8.[Web of Science][Medline]
[Order article via Infotrieve]
- Muller DN, Fischi W., Clozel J. et al. Local angiotensin II generation in the rat heart role of renin uptake. Circ Res 1998;82:13-20.[Abstract/Free Full Text]
- Chen LY, He Q., Jiang LQ, Cul CJ, Xu L., Liu LS Transgenic study of the function of chymase in heart remodeling. J Hypertens 2002;20:2047-55.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Xu J., Carretero OA, Lui YH et al. Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice. Hypertension 2002;40:244-50.[Abstract/Free Full Text]
- Horiuchi M., Akishita M., Dzau V. Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension 1999;33:613-21.[Abstract/Free Full Text]
- Lee S., Kramer CM, Mankad S., Yoo SE, Sandberg K. Combined angiotensin converting enzyme inhibition and angiotensin AT1 receptor blockade up-regulates myocardial AT2 receptors in remodeled myocardium post-infarction. Cardiovasc Res 2001;51:131-9.[Abstract/Free Full Text]
- Frohlich ED, Chien Y., Sesoko S., Pegram BL Relationship between dietary sodium intake, hemodynamics, and cardiac mass in SHR and WKY rats.Am JPhysiol 1993;264:R30-R34.[Web of Science][Medline]
[Order article via Infotrieve]
- Gu J-W., Anand V., Shek EW et al. Sodium induces hypertrophy of cultured myocardial myoblasts and vascular smooth muscle cells. Hypertension 1998;31:1083-7.[Abstract/Free Full Text]
- Harmsen E. Leenen FHH. Dietary sodium induced cardiac hypertrophy. Can J Physiol Pharmacol 1992;70:580-6.[Web of Science][Medline]
[Order article via Infotrieve]
- Ito K., Nakayama M., Hasan F., Yan X., Schneider MD, Lorell BH Contractile reverse and calcium regulation are depressed in myocytes from chronically unloaded hearts. Circulation 2003;107:1176-82.[Abstract/Free Full Text]
- Thompson EW, Marino TA, Uboh CE, Kent RL, Cooper IV G. Atrophy reversal and cardiocyte redifferentiation in unloaded cat myocardium. Circ Res 1984;54:367-77.[Abstract/Free Full Text]
- Meissner A., Min J-Y., Simon R. Effects of angiotensin II on inotropy and intracellular Ca2+ handling in normal and hypertrophied rat myocardium. JMol Cell Cardiol 1998;30:2507-18.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Kobayashi T., Hamada M., Okayama H., Shigematsu Y., Sumimoto T., Hiwada K. Contractile properties of left ventricular myocytes isolated from spontaneously hypertensive rats: effect of angiotensin II. J Hypertens 1995;13:1803-07.[Web of Science][Medline]
[Order article via Infotrieve]
- Cheng CP, Suzuki M., Ohte N., Wang ZM, Little WC Altered ventricular myocyte response to angiotensin II in pacing-induced heart failure. Circ Res 1996;78:880-92.[Abstract/Free Full Text]
- De Mello W. Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes. Hypertension 1998;32:976-82.[Abstract/Free Full Text]
- Schuijt MP, Danser AH Cardiac angiotensin II: an intracrine hormone? Am J Hypertens 2002;15:1109-16.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 4,
213-219 (2003)
DOI: 10.3317/jraas.2003.035
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
|
|
