Biochemical changes associated with development and reversal of cardiac hypertrophy in spontaneously hypertensive rats

Sen, Sayan; Rc, Tarazi; Bumpus, F. M.

doi:10.1093/cvr/10.2.254

Cited by 108 publications

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“…31 Some of the attributes of the SHR that confound studies of hypertension-induced hypertrophy include 1) the increased ventricular mass present from the first week of life, 32 which becomes very pronounced by 33 days of age 33 ; 2) arterial blood pressures significantly higher in SHR as compared with control Wistar-Kyoto rats as early as 14 days of age 34 ; and 3) progressive left ventricular hypertrophy in young, prehypertensive SHR. 35 " 37 Basically, the issue is that, apparently because of a strong genetic drive, SHR are probably born with cardiac hypertrophy and circulatory defects that make baseline data difficult to obtain and the identification of proper control animals difficult.…”

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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“…In contrast. Sen et al 16 indicated a significant decrease of DNA concentration in the SHR although an increased total content was shown in the young SHR. An explanation for the discrepancy is the difference in the normotensive control rats used in each experiment.…”

Section: :1mentioning

confidence: 95%

“…15 An increase of RNA content was also observed in the SHR heart. 16 " However, there are two conflicting reports concerning the amount of myocardial DNA content in the SHR. 16 l7 In previous experiments described in Part 1 (pp 864-872), it was shown that the heart weight of rats is a highly heritable trait, and that the effect of genetic factors upon cardiac enlargement is larger than that of elevated blood pressure at a young age.…”

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Heart size in inbred strains of rats. Part 2. Cardiovascular DNA and RNA contents during the development of cardiac enlargement in rats.

Tanase¹,

Yamori²,

Hansen³

et al. 1982

Hypertension

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Enlargement and nucleic acid content of the cardiovascular system of several strains (SHRSP/N, SHR/N, OM/N, M520/N) of rats were compared with the WKY/N strain in an attempt to characterize cardiac enlargement. Cardiac enlargement in rats can be due to either hypertrophy (increase in myocyte size), hyperplasia (increase in cell number including supporting tissue), or a combination of both. The sum of the indices of the degree of hypertrophy and hyperplasia calculated from the difference of the heart and aorta deoxyribonucleic acid (DNA) concentration and total DNA content between each strain and the WKY/N was almost equal to the degree of heart and aorta enlargement. The SHRSP/N revealed a striking hypertrophy of myocardial cells from the prehypertensive stage, and hyperplasia appeared gradually with the elevation of blood pressure. In contrast, the SHR/N developed a marked hyperplasia with some hypertrophy at the prehypertensive stage. Cardiac enlargement of the OM/N was attributed to both hypertrophy and hyperplasia. A large heart weight of the M520/N was recognized at only a young age, and was due almost entirely to hyperplasia. Aortic enlargements were related to hyperplasia. An increased ribonucleic acid (RNA) concentration was observed in both ventricles of the SHRSP/N, SHR/N, and M520/N rats at 4 weeks of age, and in all of the four strains at 16 weeks of age. A significantly higher RNA concentration was indicated in the aorta of three hypertensive strains of SHRSP/N, SHR/N, and OM/N at established hypertensive stage. These changes might be related to manifestations of genetic or other factors such as the effect of elevated blood pressure.

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“…3 ' 4 We, 2 ' *~7 as well as others, 8 "" have shown that factors other than blood pressure controls are involved in the development or reversal of myocardial hypertrophy in hypertension. Several hypotheses can be advanced to account for the factors) responsible for an increase in muscle mass as a result of increased protein synthesis.…”

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confidence: 94%

A factor that initiates myocardial hypertrophy in hypertension.

Sen¹,

Petscher²,

Ratliff³

1987

Hypertension

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SUMMARY A lack of correlation between blood pressure and myocardial hypertrophy was established in spontaneously hypertensive rats, suggesting that factors other than blood pressure control might be responsible for the modulation of myocardial hypertrophy. An in vitro system that is independent of blood pressure and hemodynamic effects was developed by use of isolated myocytes to study myocardial protein synthesis. The validity of this system was determined by means of morphology, by receptor integrity, and by studying the incorporation of tritiated leucine into myocyte protein (dpm/mg/hr). Addition of a supernatant of spontaneously hypertensive rat myocardial homogenate (centrifuged at 1500 g) to the myocyte system resulted in a significant increase in tritiated leucine incorporation into myocyte protein when compared with the addition of homogenates from normal controls. The protein from the homogenate was partially purified by high performance liquid chromatography. The resultant purified protein also stimulated protein synthesis by 70%. Furthermore, a significant increase in the specific activity of the transfer RNA and the rate of protein synthesis was observed after addition of homogenate from hypertrophied heart (4.02 ± 0.3 vs 7.0 ± 0.2 pmol leucine//xg protein/hr; p< 0.05). These data demonstrate the existence of a soluble factor in the hypertrophied myocardium that stimulated protein synthesis. This factor may play a key role in modulation of myocardial structure during development or regression of myocardial hypertrophy in hypertension. 3 ' 4 We, 2 ' *~7 as well as others, 8 "" have shown that factors other than blood pressure controls are involved in the development or reversal of myocardial hypertrophy in hypertension. Several hypotheses can be advanced to account for the factors) responsible for an increase in muscle mass as a result of increased protein synthesis. The most plausible hypothesis is that the mechanism resides entirely within the cells. When the heart is exposed to stress, there might be local release of a factor that triggers protein synthesis.To examine this hypothesis, it is essential to have an in vitro assay system that is independent of blood pres-

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Biochemical changes associated with development and reversal of cardiac hypertrophy in spontaneously hypertensive rats

Cited by 108 publications

References 0 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.

Heart size in inbred strains of rats. Part 2. Cardiovascular DNA and RNA contents during the development of cardiac enlargement in rats.

A factor that initiates myocardial hypertrophy in hypertension.

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