Left ventricular enzyme activities of the energy-supplying metabolism in Goldblatt-II rats

Koehler, Ulrich; Medugorac, I.

doi:10.1007/bf01851955

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…Others have shown an increase in hexokinase and a decrease in 3-hydroxybutyrate dehydrogenase activity in hypertrophied left ventricles of hypertensive rats. 48 Little is known about the effects of hypertension on the fuel selection of the heart, although the increased work load must profoundly affect myocardial energy metabolism. Studies in heart muscle homogenates suggest that there is decreased oxidation of fatty acids 26 and increased glycolysis 27 in the advanced stage of hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Effects of moderate hypertension on cardiac function and metabolism in the rabbit.

1988

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SUMMARY To study the early effects of hypertension on the heart, we examined isolated hearts from rabbits with slowly developing hypertension of up to 64 weeks in duration after unilateral nephrectomy and renal artery stenosis. Normotensive animals kept under identical conditions served as controls. Mean arterial blood pressure rose from 83 to 155 mm Hg in the hypertensive group of longest duration, but the ratio of left ventricular weight to body weight was not different between the experimental and control groups. Although left ventricular hypertrophy was not present, left ventricular peak systolic pressure of perfused hearts was significantly higher in hypertensive than in normotensive hearts. Furthermore, while in hypertensive hearts the left ventricular end-diastolic volume was increased, the peak systolic pressure did not respond to an increase in left ventricular enddiastolic volume. Functional changes were accompanied by metabolic changes in the left ventricle. Rates of glucose utilization were increased and rates of ketone body utilization were decreased hi hypertensive hearts. Activities of key enzymes of carbohydrate metabolism (phosphorylase, hexokinase, phosphofructokinase, and lactate dehydrogenase) were increased, while those of ketone body metabolism (3-oxoacid-CoA transferase, acetoacetyl-CoA synthase) were decreased and those of the citric acid cycle (citrate synthase, 2-oxoglutarate dehydrogenase) were not different between groups. In summary, moderate hypertension for a period of more than 1 year resulted in functional and metabolic changes of the left ventricle in hypertensive animals that were already manifest at 8 weeks of hypertension. The mechanism for the structural and functional adaptations that characterize the response of the left ventricle to hypertension may rest in changes of enzyme activities and resultant changes in substrate supply of the heart. (Hypertension 11: 416-426, 1988) KEY WORDS • renovascular hypertension activities * left ventricular function H YPERTENSION increases cardiac work by increasing plasma volume and peripheral vascular resistance. Sustained hypertension leads to changes in cardiac function and energy metabolism and, ultimately, to the development of cardiac hypertrophy. Adaptation of the heart to a high cardiac work load is important for survival of the organism as a whole and is governed by derepression of genetic information, leading to new synthesis of contractile proteins, mitochondria, and enzyme systems of myocardial energy production. Received February 17, 1987; accepted December 23, 1987. cardiac substrate metabolism • cardiac enzyme Acute pressure overload of the heart in experiments using banding of either the pulmonary artery or the aorta leads to rapid development of hypertrophy and a decrease in contractility in isolated papillary muscles, as measured by the rate of force development and the velocity of shortening by extrapolation to zero stress. 1More recent studies have reported decreased tensiondependent heat production and actin-act...

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Section: Discussionmentioning

confidence: 99%

Effects of moderate hypertension on cardiac function and metabolism in the rabbit.

1988

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“…Previous studies indicate that the activity and/or isoform distribution of a number of enzymes (e.g. hexokinase, lactate dehydrogenase, creatine kinase) alter during the development of hypertrophy [53,92,101]. The positions in the metabolic pathways of the major proteins discussed in this review are schematically shown in Fig.…”

Section: Metabolic Remodelling During Cardiac Hypertrophymentioning

confidence: 97%

Transcriptional regulation of metabolic processes: implications for cardiac metabolism

Bilsen¹,

Vusse²,

Reneman³

1998

Pfl�gers Archiv European Journal of Physiology

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Under normal conditions the oxidation of fatty acids and glucose covers, respectively, approximately 65% and 30% of the energy demand of the beating heart. Evidence is accumulating that various pathophysiological conditions are associated with overt changes in cardiac energy metabolism. For instance, in diabetes cardiac energy conversion relies even more on fatty acid than on glucose oxidation. In contrast, during cardiac hypertrophy the opposite takes place, i. e. the utilization of carbohydrates increases at the expense of lipids. The mechanisms responsible for and the significance of these metabolic adaptations are largely unknown. A growing body of evidence indicates that these metabolic adaptations are brought about, at least in part, through adjustments in the rate of transcription of genes encoding proteins involved in substrate transport and metabolism. There are reasons to believe that the transcriptional regulation of these "metabolic genes" is subject to modulation by metabolites per se, i.e. by oxygen, glucose and fatty acids. In this review the concept of metabolic remodelling as an important facet of cardiac adaptation to chronic pathophysiological conditions is introduced and the putative roles of metabolites in transcriptional regulation in the heart are considered.

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“…Increased levels and activity of HK have been measured in hypertrophied hearts. [130] Moreover, it was recently shown in transgenic mouse models that overexpressing HK2 attenuated the response to a hypertrophic stimulus, [92] and, conversely, knocking down HK2 increased susceptibility [131]. HK’s role in promoting antioxidant function via the pentose phosphate pathway (Fig.…”

Section: Hk and Metabolic Profiles In Cancer Developing Hearts And mentioning

confidence: 99%

Hexokinases and cardioprotection

Calmettes¹,

Ribalet²,

John³

et al. 2015

Journal of Molecular and Cellular Cardiology

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As mediators of the first enzymatic step in glucose metabolism, hexokinases (HKs) orchestrate a variety of catabolic and anabolic uses of glucose, regulate antioxidant power by generating NADPH for glutathione reduction, and modulate cell death processes by directly interacting with the voltage-dependent anion channel (VDAC), a regulatory component of the mitochondrial permeability transition pore (mPTP). Here we summarize the current state-of-knowledge about HKs and their role in protecting the heart from ischemia/reperfusion (I/R) injury, reviewing: 1) the properties of different HK isoforms and how their function is regulated by their subcellular localization; 2) how HKs modulate glucose metabolism and energy production during I/R; 3) the molecular mechanisms by which HKs influence mPTP opening and cellular injury during I/R; 4) how different metabolic and HK profiles correlate with susceptibility to I/R injury and cardioprotective efficacy in cancer cells, neonatal hearts, and normal, hypertrophied and failing adult hearts, and how these difference may guide novel therapeutic strategies to limit I/R injury in the heart.

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Left ventricular enzyme activities of the energy-supplying metabolism in Goldblatt-II rats

Cited by 14 publications

References 39 publications

Effects of moderate hypertension on cardiac function and metabolism in the rabbit.

Effects of moderate hypertension on cardiac function and metabolism in the rabbit.

Transcriptional regulation of metabolic processes: implications for cardiac metabolism

Hexokinases and cardioprotection

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