Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat.

Isoyama, Shogen; Wei, Jeanne Y.; Izumo, Seigo; Fort, Patrice E.; Schöen, Frederick J.; Grossman, William

doi:10.1161/01.res.61.3.337

Cited by 88 publications

(62 citation statements)

References 35 publications

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“…(iii) Ascending aortic coarctation group. To analyze the response to acute pressure overload, ascending aortic coarctation (n = 12) was produced as described (6). For group ii and iii sham-operated animals (n = 12) that had identical procedures done with the exception of aortic constriction were used as controls.…”

Section: Methodsmentioning

confidence: 99%

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Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.

Izumo

Nadal‐Ginard

Mahdavi

1988

Proc. Natl. Acad. Sci. U.S.A.

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792

388

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Hypertrophy, an increase in cell size without cell division, is a fundamental adaptive process employed by postmitotic cardiac and skeletal muscle cells. Cardiac myosins undergo an adult-to-fetal isoform transition in various models of hypertrophy. Using gene-specific cDNA probes, we show here that in the adult myocardium the mRNAs encoding the fetal (skeletal muscle type) isoforms of a-actin and sarcomeric tropomyosin are re-expressed within 2 days in response to pressure overload. In addition, atrial natriuretic factor mRNA, so far believed to be expressed primarily in the atria, was readily detectable in the ventricles of neonates and was induced to markedly high levels in pressure-overloaded adult ventricles. In contrast, cardiac hypertrophy produced by thyroid hormone excess was not associated with induction of the atrial natriuretic factor gene or fetal contractile protein isogenes. Furthermore, the c-fos and c-myc protooncogenes and a major heat shock protein gene (hsp7O) are induced in the ventricular myocardium within 1 hr after imposition of pressure overload. These results suggest that induction of cellular protooncogenes and heat shock (stress) protein genes is an early response to pressure overload, whereas reinduction of the genes normally expressed only in perinatal life, such as fetal isoforms of contractile proteins and atrial natriuretic factor, is a later event. These two types of responses might represent the general pattern of growth induction to work overload by terminally differentiated cells that have lost the ability to undergo DNA replication.The cardiac response to normal growth requirements, as well as to work overload, is dependent on the developmental stage of the organ. During fetal and early postnatal life, the demand for an increased cardiac mass is fulfilled mainly by an increase in the number of preexisting myocytes (hyperplasia), whereas later in life demand for increased mass is fulfilled exclusively by an increase in the size of a fixed number of preexisting myocytes (hypertrophy) (1). Although the most striking feature of the cardiac hypertrophic response is quantitative, resulting in the addition of new sarcomere units within the cell, there are also qualitative changes in the composition of contractile proteins in hypertrophic cells. Myocardial hypertrophy has been shown to be associated with either normal, depressed, or increased contractility, depending on the particular model of hypertrophy studied (2): (i) normal cardiac growth or physiologic hypertrophy from neonatal-to-adult stages, in which the contractility of the myocardium remains normal; (ii) pathologic hypertrophy due to acute pressure overload in which the ventricular weight increases, and the contractility per unit of myocardium is depressed; and (iii) supraphysiologic hypertrophy induced by thyroid hormone excess, in which the increase in myocardial mass is associated with an increase in contractility.It has been previously shown that, in the rat, work overload-induced hypertrophy induces a myosin h...

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Section: Methodsmentioning

confidence: 99%

“…For the fetal and neonatal animals, right and left ventricles were harvested together, whereas in the case of adult animals, only the left ventricle, including the ventricular septum, was dissected. Total cellular RNA was extracted by a modification of the hot phenol procedure (6). RNA blot analysis was done in a standard manner (7).…”

Section: Methodsmentioning

confidence: 99%

Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.

Izumo

Nadal‐Ginard

Mahdavi

1988

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

792

388

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“…It was impossible to examine the response of the myocardium and coronary vasculature to more severe pressure overload because more severe loading might have produced an extremely high mortality in old rats, as mentioned in the previous study of Isoyama et al 10 The data in this study show myocardial hypertrophic response and coronary hemodynamic response to relatively mild pressure overload in the two age groups. We should emphasize that even mild pressure overload caused abnormalities of the coronary circulation in the absence of significant myocardial hypertrophy in the aged group.…”

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confidence: 63%

“…For each section, a mean myocyte width was determined by measurement of transnuclear widths of random, longitudinally oriented myocytes in the circular midwall bundles with a calibrated microscope eyepiece reticle (10 cells for each sample) on random fields at a magnification of x400. 10 In the right ventricle, myocardial sections were cut in planes perpendicular and parallel to the apex-to-base axis. A mean myocyte width was obtained in those samples as was done in the left ventricle.…”

Section: Histological Examinationmentioning

confidence: 99%

Effect of age on coronary circulation after imposition of pressure-overload in rats.

1991

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We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 ±7 mm Hg in sham-operated rats versus 160 ±11 mm Hg in banded rats of the young adult group; 103 ±7 mm Hg in sham-operated rats versus 156±11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy. These coronary vascular changes as well as diminished hypertrophic response may explain the high incidence of heart failure or ischemic episodes during chronic hemodynamic stress in aged patients. Address for reprints: Tamotsu Takishima, MD, First Department of Internal Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai 980, Japan.Received February 19, 1990; accepted in revised form November 6, 1990. creases in shortening velocity have been reported at organ and muscle levels.413 -17 Furthermore, the capacity for myocardial hypertrophy to develop in response to chronic pressure-or volume-overload is diminished in aged subjects compared with younger adults. 10-11 -18 -19 At present, however, there is no information concerning the coronary vascular response to stress from chronic pressure overload in aged subjects.Abnormalities of the coronary circulation in pressure-overloaded hearts are caused by hypertensive vascular changes 20 -21 as well as by the presence of myocardial hypertrophy. 22-24 Therefore, even if a similar pressure-overload stress is applied to young adult and old subjects, the stress may produce different effects on coronary circulation between young and old subjects directly through underlying agerelated changes in coronary vasculature or indirectly through the diminished myocardial hypertrophic response. To test this hypothesis, we examined the effects of pr...

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“…24 - 27 Each rat was anesthetized with pentobarbital sodium (50 mg/kg i.p.) and endotracheal intubation was performed with direct visualization.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Normalization of impaired coronary circulation in hypertrophied rat hearts.

1990

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We tested the hypothesis that impaired coronary autoregulation, decreased flow reserve, and diminished reactive hyperemic response in hypertrophied hearts with coronary arterial hypertension may be reversible after relief of pressure overload. In 4-week ascending aortic banded rats, in vivo peak systolic left ventricular pressure increased to 178±8 mm Hg (103±6 mm Hg in sham-operated control group). This increased pressure produced myocardial hypertrophy, and the left ventricular weight/body weight ratio was 46% above that of the control group. After the rats were killed, the coronary perfusion pressure-flow relations were obtained during resting conditions and maximal vasodilation after a 40-second period of ischemia in beating but nonworidng isolated hearts perfused with Tyrode's solution with bovine red blood cells and albumin. In hearts from control rats, coronary autoregulation (i. I n normal hearts, coronary blood flow decreases only slightly with reduction of perfusion pressure in the autoregulatory range. 1 In the subendocardium of hypertrophied hearts with hypertension, autoregulation is impaired in the lower range of coronary perfusion pressure.2 Furthermore, coronary flow reserve estimated with adenosine, dipyridamole, or flow increases during stress or after ischemia is also decreased in hypertrophied hearts.3 -23 In previous studies, 24 -25 we reported that the maximal coronary flow rate during reactive hyperemia decreased in cardiac hypertrophy, but the decreased flow normalized after relief of pressure overload. Also, Anderson et al 26 reported that decreased flow reserve and coronary vascular structural changes in the spontaneously hypertensive rat were reversible after antihypertensive drug administration. However, there is no information concerning the reversibility of impaired coronary autoregulation in hypertrophied hearts. In the present study, we tested the hypothesis that the impaired coronary autoregulation and diminished hyperemic response to brief ischemia may reverse after relief of pressure overload. For this purpose, we used an experimental model consisting of ascending aortic banding and debanding in the rat. After isolation of the heart, we studied coronary hemodynamics in beating but nonworking hearts perfused with Tyrode's solution with bovine red blood cells and albumin because coronary autoregulation depends on myocardial metabolism.1 Moreover, because coronary flow reserve depends on coronary perfusion pressure, 118 we attempted to determine coronary flow reserve from coronary pressure-flow relations during resting conditions and during maximal vasodilation after brief ischemia. MethodsWe used male Wistar rats 6-8 weeks old. After opening the chest, we banded the ascending aorta. Four weeks after banding, we operated on the rats again for the purpose of debanding some of them. We studied coronary hemodynamics in the following

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Effect of age on the development of cardiac hypertrophy produced by aortic constriction in the rat.

Cited by 88 publications

References 35 publications

Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.

Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.

Effect of age on coronary circulation after imposition of pressure-overload in rats.

Normalization of impaired coronary circulation in hypertrophied rat hearts.

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