Circulation Research, Vol 67, 1334-1344, Copyright © 1990 by American Heart Association

ARTICLES

Regional changes in creatine kinase and myocyte size in hypertensive and nonhypertensive cardiac hypertrophy

SH Smith, MF Kramer, I Reis, SP Bishop and JS Ingwall
Department of Pathology, University of Alabama, Birmingham 35294.

Several intracellular enzymes have been shown to have altered total activity or isoenzyme composition in cardiac hypertrophy. This study tests the hypothesis that the accumulation of the fetal-type (BB + MB) creatine kinase (CK) isoenzymes in hypertrophied adult myocardium is related to an increase in blood pressure. Consideration was made for the location, size, and hemodynamic load of the myocytes. By using the two-kidney, one-clip (2K1C) rat model of renal hypertension with and without hydralazine treatment, CK (total and isoenzyme), lactate dehydrogenase, and citrate synthase activities and myocyte size were measured. An increased heart weight/body weight ratio occurred in both untreated 2K1C rats (4.15 +/- 0.09) and hydralazine-treated 2K1C rats (4.12 +/- 0.13) as compared with control rats (3.25 +/- 0.10). Blood pressure was high only in untreated 2K1C rats (196 +/- 9 mm Hg), as compared with hydralazine-treated 2K1C rats (142 +/- 6 mm Hg) and control rats (135 +/- 3 mm Hg). Myocytes were isolated from five ventricular regions: left ventricular epicardial and endocardial free wall, left and right halves of the interventricular septum, and right ventricular free wall. Regional differences in normal and hypertrophied myocardium were demonstrated for morphological and biochemical parameters, with the greatest changes occurring in left ventricular endocardium. The shift in CK isoenzyme expression toward accumulating more BB + MB was greater in "hypertensive hypertrophy" (untreated 2K1C rats) than in "nonhypertensive hypertrophy" (hydralazine-treated 2K1C rats). Calculations incorporating isolated myocyte volume showed that the cellular content of total CK remained the same during the hypertrophic process, accounting for a decrease in the tissue activity. Measurement of lactate dehydrogenase and citrate synthase activities suggests that hypertrophied myocardium has relatively higher glycolytic capacity and that this effect is exacerbated in the presence of high blood pressure. We conclude that increased blood pressure is more closely linked to the fetal CK isoenzyme shift than is hypertrophy alone.

This article has been cited by other articles:

				L. S. Kang, R. A. Reyes, and J. M. Muller-Delp Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2 Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H1087 - H1095. [Abstract] [Full Text] [PDF]

				C. S. Smith, P. A. Bottomley, S. P. Schulman, G. Gerstenblith, and R. G. Weiss Altered Creatine Kinase Adenosine Triphosphate Kinetics in Failing Hypertrophied Human Myocardium Circulation, September 12, 2006; 114(11): 1151 - 1158. [Abstract] [Full Text] [PDF]

				J. S. Ingwall and R. G. Weiss Is the Failing Heart Energy Starved?: On Using Chemical Energy to Support Cardiac Function Circ. Res., July 23, 2004; 95(2): 135 - 145. [Abstract] [Full Text] [PDF]

				S. J. Park, J. Zhang, Y. Ye, S. Ormaza, P. Liang, A. J. Bank, L. W. Miller, and R. J. Bache Myocardial creatine kinase expression after left ventricular assist device support J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1773 - 1779. [Abstract] [Full Text] [PDF]

				U. K. M. Decking, C. Alves, T. Wallimann, M. Wyss, and J. Schrader Functional aspects of creatine kinase isoenzymes in endothelial cells Am J Physiol Cell Physiol, July 1, 2001; 281(1): C320 - C328. [Abstract] [Full Text] [PDF]

				A. Natali, D. Turner, S. Harrison, and E White Regional effects of voluntary exercise on cell size and contraction-frequency responses in rat cardiac myocytes J. Exp. Biol., January 3, 2001; 204(6): 1191 - 1199. [Abstract] [PDF]

				F. Muders, S. Neubauer, A. Luchner, S. Fredersdorf, G. Ickenstein, G. A.J. Riegger, M. Horn, and D. Elsner Alterations in myocardial creatinine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme-distribution in a model of left ventricular dysfunction Eur J Heart Fail, January 1, 2001; 3(1): 1 - 5. [Abstract] [Full Text] [PDF]

				M. Wyss and R. Kaddurah-Daouk Creatine and Creatinine Metabolism Physiol Rev, July 1, 2000; 80(3): 1107 - 1213. [Abstract] [Full Text] [PDF]

				D. O. Wilson and P. Johnson Exercise modulates antioxidant enzyme gene expression in rat myocardium and liver J Appl Physiol, May 1, 2000; 88(5): 1791 - 1796. [Abstract] [Full Text] [PDF]

				D. G. Simpson, M. Majeski, T. K. Borg, and L. Terracio Regulation of Cardiac Myocyte Protein Turnover and Myofibrillar Structure In Vitro by Specific Directions of Stretch Circ. Res., November 12, 1999; 85 (10): e59 - e69. [Abstract] [Full Text] [PDF]

				Y. Goldberg, G. Taimor, H. M. Piper, and K.-D. Schluter Intracellular signaling leads to the hypertrophic effect of neuropeptide Y Am J Physiol Cell Physiol, November 1, 1998; 275(5): C1207 - C1215. [Abstract] [Full Text] [PDF]

				P. Yue, B. M. Massie, P. C. Simpson, and C. S. Long Cytokine expression increases in nonmyocytes from rats with postinfarction heart failure Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H250 - H258. [Abstract] [Full Text] [PDF]

				Y. M Pinto, M. Paul, and D. Ganten Lessons from rat models of hypertension: from Goldblatt to genetic engineering Cardiovasc Res, July 1, 1998; 39(1): 77 - 88. [Abstract] [Full Text] [PDF]

				R. Tian, L. Nascimben, J. S. Ingwall, and B. H. Lorell Failure to Maintain a Low ADP Concentration Impairs Diastolic Function in Hypertrophied Rat Hearts Circulation, August 19, 1997; 96(4): 1313 - 1319. [Abstract] [Full Text]

				E. O. Weinberg, M. A. Lee, M. Weigner, K. Lindpaintner, S. P. Bishop, C. R. Benedict, K. K. L. Ho, P. S. Douglas, E. Chafizadeh, and B. H. Lorell Angiotensin AT1 Receptor Inhibition : Effects on Hypertrophic Remodeling and ACE Expression in Rats With Pressure-Overload Hypertrophy due to Ascending Aortic Stenosis Circulation, March 18, 1997; 95(6): 1592 - 1600. [Abstract] [Full Text]

				B. M. Massie, S. Schaefer, J. Garcia, M. D. McKirnan, G. G. Schwartz, J. A. Wisneski, M. W. Weiner, and F. C. White Myocardial High-Energy Phosphate and Substrate Metabolism in Swine With Moderate Left Ventricular Hypertrophy Circulation, March 15, 1995; 91(6): 1814 - 1823. [Abstract] [Full Text]

				M. E. Christe and R. L. Rodgers Cardiac Glucose and Fatty Acid Oxidation in the Streptozotocin-Induced Diabetic Spontaneously Hypertensive Rat Hypertension, February 1, 1995; 25(2): 235 - 241. [Abstract] [Full Text]