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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertensive diabetic rats develop a cardiomyopathy characterized by systolic and diastolic ventricular dysfunction, myocardial hypertrophy and fibrosis, pulmonary congestion and a very high mortality rate. Alterations in contractile proteins and sarcoplasmic reticular calcium (Ca2+) transport in diabetic myocardium and their partial reversal with verapamil suggest that calcium channel blockade may prevent death from congestive heart failure in hypertensive diabetic rats. A large group of rats with renovascular hypertension and streptozotocin diabetes were divided into four groups: untreated animals (Group 1) and animals treated with 100 (Group 2), 300 (Group 3) or 600 (Group 4) mg/kg per day of sustained release diltiazem mixed in their food. Treatment was begun shortly after the onset of hypertension and diabetes. Mortality rates after 4 months were 59% (19 of 32), 53% (17 of 32), 27% (7 of 26) and 35% (12 of 34) in Groups 1, 2, 3 and 4, respectively; the mortality rate in age-matched control rats was 5% (1 of 19). The reductions in mortality rates in Groups 3 and 4 were statistically significant. Diltiazem did not change systolic blood pressure, serum glucose concentration, heart rate or left ventricular mass. There was a trend to decreased left ventricular interstitial fibrosis and perivascular fibrosis in diltiazem-treated animals. Ventricular collagen concentration was similar in untreated hypertensive diabetic and control rats; levels were higher in hypertensive diabetic rats that died than in those that survived. There was a trend to decreased collagen concentration as diltiazem dose increased. Myosin isoenzyme distribution was not changed in Groups 3 and 4 (in comparison with Group 1). In all hypertensive diabetic groups, rats that died had a higher blood pressure, heart rate, relative left ventricular mass, lung weight and lung water than did survivors. The mortality rate was two to three times higher among rats with an initial blood pressure greater than or equal to 180 mm Hg. The beneficial effects of diltiazem on survival were most significant among rats with severe hypertension.
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PMID:Beneficial effects of diltiazem on the natural history of hypertensive diabetic cardiomyopathy in rats. 183 34

The mechanisms by which the aged heart adapts to a superimposed pressure load such as hypertension have not been described. We therefore investigated biochemical and molecular genetic adaptations in the 24-month-old rat heart subjected to renovascular hypertension. Compared with 4-month-old rats, aging was associated with a 68% increase in left ventricular mass without any change in heart weight-to-body weight ratio, a 33% reduction in calcium-activated myosin ATPase activity, and a shift from a V1 to a V3 predominant myosin heavy chain (MHC) isoform distribution. A 46% reduction in alpha-MHC mRNA and a reciprocal increase in beta-MHC mRNA was seen. When hypertension was superimposed, there was a further 75% increase in ventricular mass, a 63% increase in heart weight-to-body weight ratio, and a 19% reduction in myosin ATPase. Myosin isozyme distribution was further shifted to V3, and the ratio of alpha-MHC to beta-MHC mRNA was reduced. In addition, with hypertension a significant (greater than 50%) reduction in the mRNA level of the cardiac sarcoplasmic reticular calcium-activated ATPase was seen. These data demonstrate that the aged myocardium is able to respond to a superimposed pressure load with a molecular genetic and protein synthetic pattern of hypertrophy analogous to that seen in younger animals.
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PMID:Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart. 183 8

After myocardial infarction in rats, muscle performance in the remaining hypertrophied myocardium deteriorates and is associated with a decrease in myosin adenosinetriphosphatase (ATPase) activity and a shift to the V3 myosin heavy-chain isoform. We have previously shown in another model of hypertrophy, secondary to renovascular hypertension, that chronic intermittent adrenergic stimulation with dobutamine (Db) can prevent this biochemical adaptation. The present study was undertaken to assess the effects of chronic Db treatment on cardiac mass, function, metabolism, and myosin biochemistry in animals subjected to chronic myocardial infarction. Four groups of rats were studied: controls, animals treated with Db (2 mg/kg 2X daily for 4 wk), animals subjected to myocardial infarction and killed after 4 wk (MI), and MI animals concurrently treated with Db for 4 wk (MI-Db). The two MI groups were subdivided into those with and without congestive heart failure (CHF). Heart weight was increased by 13% with Db, unchanged in the infarct groups without CHF, and increased by 9 and 22% in the infarct groups with CHF. Db did not have any additional effect on heart weight in these later groups. Infarct weight was greatest in the animals with CHF, and viable myocardium was equivalent in all infarct groups suggesting that CHF was associated with a greater degree of hypertrophy. Ventricular performance, as assessed in an isovolumic heart apparatus, was markedly depressed in both infarct groups with CHF and was not affected by Db. Db increased myosin ATPase activity in control and infarcted animals both with and without congestive heart failure. Myosin oxygen consumption and lactate production were not adversely affected by Db.
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PMID:Effects of chronic dobutamine on cardiac mechanics and biochemistry after myocardial infarction in rats. 199 90

The purpose of this study was to determine whether a chronic swimming program could reverse the decreased cardiac function and altered myosin biochemistry found in hearts of rats with established renal hypertension. Ten wk after the onset of hypertension [midpoint (m)], hearts from normotensive controls (C) and hypertensives (H) were studied in an isolated working heart apparatus, and myosin biochemistry was analyzed. Half of the control and hypertensive animals were then subjected to a 10-wk swimming program (Sw) and their hearts were compared with those from age-matched sedentary rats. Body weight was no different at the midpoint of the study between Cm and Hm or at the end point (e) of the study among Ce, Swe, He, or H-Swe. Swimming had no effect on blood pressure in either normotensive or hypertensive rats. Dry heart weight was increased by 46% in Hm compared with Cm and by 36% in He, 21% in Swe, and 61% in H-Swe when compared with Ce. Hypertension was associated in both the mid- and end-point studies, with decreases in coronary flow, stroke work (both per gram left ventricle), ejection fraction, and midwall fractional shortening. In addition, actin-activated myosin adenosinetriphosphatase (ATPase) activity was decreased in Hm and He associated with an increase in the content of the V3 myosin isoenzyme. Although the coronary deficit was not corrected in H-Swe, stroke work, ejection fraction, and fractional midwall shortening were normalized compared with control hearts. Myosin ATPase activity and the myosin isoenzyme distribution were similarly restored in H-Swe.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic swimming reverses cardiac dysfunction and myosin abnormalities in hypertensive rats. 293 53

To determine whether a prior chronic swimming program would alter the heart's response to chronic hypertension, female rats were made to swim for 10 wk, and then the left renal artery was stenosed. Heart perfusions were performed 10 wk later. The five groups studied were: control (C), normotensive swimmers (Sw), sedentary hypertensives (H), swimming rats made hypertensive and then allowed to be sedentary (Sw-H-Sd); and swimming animals made hypertensive and continued in a swimming program (Sw-H-Sw). Total heart and left ventricular weights were increased in increasing degrees in the sequence Sw, H, Sw-H-Sd, and Sw-H-Sw. Right ventricular weight was only increased in Sw and Sw-H-Sw. Swimming before the onset of hypertension enhanced total cardiac output and stroke work. Ejection fractions and mean velocity of circumferential fiber shortening (Vcf) were increased in Sw-H-Sd or Sw-H-Sw vs. controls. Myocardial O2 extraction was increased and coronary flow and myocardial O2 consumption were diminished in all hypertensive groups. However, lactate production was similar in all groups. Myosin adenosinetriphosphatase activity was increased in Sw but decreased in the three H groups. The percent of V1 myosin isozyme was greater and the percent of V3 less in Sw than in C; V1 was diminished and V3 increased in H and Sw-H-Sd; isozymes were normal in Sw-H-Sw.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hypertension on hearts of rats trained by swimming. 295 61

The effect of angiotensin II-induced hypertension on selected biochemical parameters was studied in Sprague-Dawley rats. Angiotensin II infusion at rates of 41.7 micrograms h-1 kg-1 and 12.5 micrograms h-1 kg-1 for 2, 5, 10 and 15 days elevated the systolic blood pressure from 143 +/- 7 mmHg to 215-230 mmHg (P less than 0.001) and 185-195 mmHg (P less than 0.001), respectively. The left ventricular weight/body weight ratio increased 10-14% (P less than 0.05) and 23-32% (P less than 0.001) after 2-15 days in rats treated at the lower and higher infusion rates, respectively. Prolyl 4-hydroxylase (PH) activity, a marker of collagen synthesis, was evenly distributed in the left ventricle. PH activity increased by about 100% in both subendocardial and subepicardial layers of the left ventricular wall after angiotensin II infusion for 10 days at 41.7 micrograms h-1 kg-1, but remained unaltered at 12.5 micrograms h-1 kg-1. No change was observed in hydroxyproline concentration. Myosin isoenzymes (V1-V3), which reflect myocardial contractility, were unevenly distributed in the left ventricular wall: the proportion of the fast-turnover isoenzyme (V1) was smaller in the subendocardial layer than in the subepicardial layer. The proportion of V1 decreased after treatment in both layers. Alkaline phosphatase activity, a marker of capillary density, was evenly distributed transmurally in the left ventricular wall. Angiotensin II caused a slight decrease in this activity in both myocardial layers. The results suggest that the elevation of blood pressure leads to transmurally evenly distributed changes in biochemical parameters reflecting collagen synthesis, capillary density and contractile properties of the myocardium.
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PMID:Transmural distribution of biochemical markers of total protein and collagen synthesis, myocardial contraction speed and capillary density in the rat left ventricle in angiotensin II-induced hypertension. 297 33

The significance of various factors for the development of structural dilatation in the chronically pressure-loaded and failing heart were evaluated. The investigations were performed on male rats with renal (Goldblatt II) and spontaneous (Aoki-Okamoto) hypertension at different stages of haemodynamic overload. Two groups of SHR were submitted to intermittent feeding (SHR IF); one group received additionally the beta-blocking agent atenolol (50 mg/kg b.w.; SHR IF + beta Bl.). Haemodynamic measurements were carried out under open chest conditions. Myosin isoenzyme pattern, hydroxyproline concentration and circulating blood volume were determined. Transformation to slower myocardium per se, induced by IF, did not lead to significant change in ventricular configuration. After additional blockade of beta-adrenergic receptors there were indications of unfavourable development of left ventricular configuration. Inhibition of hypertrophic mass increase due to curtailed adrenergic stimulation could be an influential factor in the development of dilatation. Further investigations, however, are required to establish the relationship between the adrenergic system, on the one hand, and degree of hypertrophy as well as structural dilatation of the ventricle, on the other hand. The established marked increase in hydroxyproline concentration of the dilated ventricle of SHR in congestive failure is consistent with the assumption of a causal link between the degree of fibrosis and structural dilatation. Observations on rats with aorto-caval shunt and Goldblatt II rats with eccentric hypertrophy and corresponding increase in filling potential or circulating blood volume indicate a correlation between the latter and ventricular size. Thus, we assume that curtailed protein synthesis, fibrosis and regulatory processes related to water and electrolyte balance, but not myocardial transformation per se, play a role in the development of structural dilatation. The relative contribution of each factor, however, may depend on the experimental model that is used.
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PMID:Chronic cardiac reactions. III. Factors involved in the development of structural dilatation. 366 15

To evaluate the combined effects of cardiac overload imposed by hypertension and by chronic exercise, male and female rats were made hypertensive by unilateral renal artery stenoses and made to exercise in an 8-10-wk swimming program. Sedentary normotensive animals, sedentary hypertensive animals and normotensive animals exposed to the swimming program were also studied. Hypertension was associated with the development of cardiac hypertrophy, and this was exaggerated in hypertensive swimmers. Actomyosin, Ca2+-myosin, and actin-activated Mg2+-myosin ATPase activities were enhanced in normotensive swimmers, depressed in hypertensives and were normal or increased in hypertensive swimmers. Myosin isoenzyme analysis showed a predominant V1 pattern in normals; an increase in percent V1 isoenzyme is swimmers; a predominant V3 pattern in hypertensives; and a return to the predominant V1 pattern in hypertensive swimmers. These findings suggest that the hypertrophy imposed by hypertension and hypertrophy imposed by physical training using a chronic swimming program are distinctly different biological phenomena. Physical training by swimming prevents the changes in cardiac myosin induced by hypertension despite the exaggeration of hypertrophy.
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PMID:Physiologic cardiac hypertrophy corrects contractile protein abnormalities associated with pathologic hypertrophy in rats. 621 15

To explore the interactions of physiologic and pathologic hypertrophy, four groups of hearts were studied in an isolated working rat heart apparatus. Cardiac contractile proteins were also evaluated. The groups were hearts of female control sedentary rats; rats subjected to a 10-week swimming programme; rats with renal hypertension; and hypertensive rats subjected to a 10-week swimming programme. The swimming programme in normotensive female rats caused a 30% cardiac hypertrophy, in hypertensive animals 46% hypertrophy, and in combined hypertension and swimming 70% hypertrophy. Ca2+-myosin ATPase activity and actin-activated myosin ATPase were elevated in hearts of swimmers, depressed in hearts of hypertensive sedentary animals and similar to control values in hearts of hypertensive swimmers. Myosin V1 isoenzyme content was increased in hearts of swimmers, depressed in hearts of hypertensives, but normal in hearts of hypertensive swimmers. Reciprocal relationships were seen with the V3 isoenzyme. Stroke work, mean velocity of circumferential fibre shortening, and per cent fractional shortening at the midwall showed increased values for hearts of swimmers, depressed values for hearts of hypertensives, and normal values or values above the control for hearts of hypertensive swimmers. Myocardial flow measured with microspheres was increased in the left ventricle of swimmers, depressed in hearts of hypertensives and still depressed in hypertensive swimmers, but significantly higher than in the hypertensives alone. The correlation of actin-activated ATPase activity and of fractional shortening was linear among the four groups. These studies demonstrate that physiologic and pathologic hypertrophy in the rat have distinctly opposite effects on contractile proteins and contractile performance. When one type of hypertrophy is superimposed on the other the effects are additive.
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PMID:Correlation of myosin isoenzyme alterations with myocardial function in physiologic and pathologic hypertrophy. 624 4

The heart is a major target organ for thyroid hormone action, and marked changes occur in cardiac function in patients with hypothyroidism or hyperthyroidism. Triiodothyronine (T3)-induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independently of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, T3 leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart. The pathophysiologic basis for myxedema is the opposite of that discussed for the hyperthyroid heart. In addition to decreased direct effects of thyroid hormone in cardiac myocytes, indirect effects occur through decreases in peripheral oxygen consumption and changes in hemodynamic parameters. Myofibrillar swelling with loss of striation and interstitial fibrosis occurs on histologic examination of hypothyroid hearts. In addition, accumulation of mucopolysaccharide substances (Glycosaminoglycans) can be demonstrated. On electron microscopic examination, mitochondria show disruption and lipid inclusion. Cardiac papillary muscle obtained from animals with hypothyroidism shows a depression of the force velocity curve and reduced rate of tension development, indicating significant contractile abnormalities. In patients with hypothyroidism, a true enhanced incidence of hypertension (increased peripheral vascular resistance) has been found. In addition, hypercholesterolemia and impairment of fatty acid mobilization are associated with myxedema and present additional risk factors for the development of atherosclerotic cardiovascular disease.
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PMID:[Cardiovascular effects of thyroid hormones]. 906 69


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