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

Abstract

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.

Aging impairs flow-induced dilation in coronary arterioles: role of NO and H2O2

“…It is notable that the septal artery is derived from a superficial portion of the right ventricular side of the septal wall, whereas, in the present study, vessels were obtained from within the left ventricular free wall. Previous studies have demonstrated increased glycolytic activity in left ventricle vs. septal tissue samples from bovine and rat hearts (36,42). Therefore, it is possible that differences in metabolic demand of these vascular beds may contribute to the variant findings.…”

Is the Failing Heart Energy Starved?

“…This is wellillustrated by an early study in which cell size and enzyme activities of several proteins known to change in cardiac hypertrophy and failure were measured in myocytes isolated from different regions of hypertensive and nonhypertensive hypertrophied rat hearts (2 kidney, 1 clip model). 57 Some proteins increased in proportion to myocyte size while others were relatively diluted, and still others increased out of proportion to myocyte size. Regulation of gene expression differed among neighboring cells within the same organ.…”

Altered Creatine Kinase Adenosine Triphosphate Kinetics in Failing Hypertrophied Human Myocardium

“…Specific cytosolic and mitochondrial isoforms of CK maintain high ATP/ADP ratios at the myofibrillar sites of utilization and low ATP/ADP ratios at the mitochondrial sites of production. The CK cytosolic isozyme shift to more "fetal" isoforms in LVH models 7,14,15 and in human LVH 4 is postulated to offer a thermodynamic advantage. CK isoform analysis could not be performed in the present noninvasive study of stable ambulatory patients with LVH because there was no clinical indication for the requisite cardiac biopsy.…”

“…4,5 The PCr/ATP ratio is one indicator of the energetic state of the myocardium and is reduced in animal models of myocardial hypertrophy, 6,7 in human LVH, 8 -10 and in CHF. 11,12 Despite the potential importance of the cardiac PCr/ATP ratio for understanding cardiac energetics, this ratio does not directly reflect the rate of ATP production through the CK reaction, 7,[13][14][15] which may be more important in the progression to CHF in patients with LVH.…”