Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of converting enzyme inhibition on the cardiac mass, isomyosins polymorphism, and collagen network in the left ventricle have been studied in renovascular, hypertensive, spontaneously hypertensive, and normotensive rats. The isoenzyme profile of left ventricular myosins was used as an indirect marker of the intrinsic property of contractility, whereas the collagen network, measured by a morphometric method, represented an indirect structural marker of the arrhythmogenic risk. One-clip, two-kidney renovascular hypertension was associated with cardiac hypertrophy, a shift in the isomyosin profile, and accumulation of collagen within the left ventricular myocardium. In this renin-angiotensin-dependent model, one month of treatment with converting enzyme inhibitor normalized blood pressure and consistently reversed cardiac hypertrophy and the isomyosin profile. Converting enzyme inhibitor treatment of 12-week-old spontaneously hypertensive rats for three months significantly decreased blood pressure but did not completely normalize it. The increase in cardiac mass observed in spontaneously hypertensive rats was not reversed by this short treatment. Nevertheless, the percentage of the V1 form of myosin increased slightly after treatment, and the collagen content of the left ventricle was considerably decreased. Converting enzyme inhibition did not decrease blood pressure in DOCA-salt hypertension, and no changes were observed in cardiac hypertrophy, isomyosin profile, or the collagen network. The cardiac hypertrophy that occurs with aging in normotensive rats was associated with a significant shift in isomyosin profile and a large accumulation of collagen. Thus, aging mimics several of the quantitative and qualitative changes in the left ventricular protein profile observed in hypertension. In young normotensive rats, converting enzyme inhibition significantly decreased blood pressure and left ventricular mass, increased the percentage of V1 isomyosin, and prevented the accumulation of collagen. In one-year-old normotensive rats, treatment for six months with converting enzyme inhibitor decreased blood pressure, decreased cardiac mass, and prevented the accumulation of collagen; the isomyosin profile was not modified. Converting enzyme inhibition, by acting on cardiac afterload, can bring about quantitative and qualitative changes in the cardiac proteins of both hypertensive and normotensive rats.
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PMID:Myocardial effect of converting enzyme inhibition in hypertensive and normotensive rats. 297 59

In hypertension, the heart of small mammals can express different isoenzymic forms of proteins under the influence of overload and other modulating factors. The increase in ventricular mass is generally paralleled by progressive changes in the isoforms of at least two proteins that are involved in the contraction process, namely, myosin and creatine-kinase. This review summarizes the biochemical and molecular changes occurring during progression and with regression of cardiac hypertrophy in rats, humans, and other animals, and focuses on the role played by antihypertensive drugs in modulation of ventricular isomyosins. The implications of these observations for humans remain to be fully determined.
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PMID:Left ventricular hypertrophy in hypertension. Changes in isomyosins and creatine-kinase isoenzymes. 297 60

The structural and functional characteristics of the myocardium and coronary vessels are major determinants of cardiac function. Both can be influenced by long-term hemodynamic changes, such as sustained alterations of pressure and/or volume load on the heart. The diastolic pressure-volume relationship of the left ventricle (LV) was evaluated in arrested isolated hearts from spontaneously hypertensive rats (SHR), Wistar Kyoto normotensive rats (WKY), pregnant and hyperthyroid SHR and WKY. Such measurements of the LV dimensions were also performed after antihypertensive therapy by hydralazine, felodipine, metoprolol and alpha-methyldopa. Cardiac function was studied in a perfusion system in which external work could be measured at various pre- and afterloads. Coronary flow and O2-extraction could also be determined. LV function was examined in young and aged SHR and WKY, in metoprolol-felodipine treated SHR and in two-kidney, one clip hypertension before and after its reversal by renal artery unclipping. The SHR LV in early established primary hypertension mainly showed eccentric hypertrophy, with increased LV enddiastolic volume for a given filling pressure and a marginal reduction of wall to lumen ratio (w/ri). Hence, a higher stroke volume could be delivered for a given myocardial fibre shortening. Nevertheless, when challenged by high afterloads, LV function in SHR was considerably augmented compared with WKY. The antihypertensive drugs used reduce arterial pressure in different ways, which may differently affect cardiac design. Generally, the results suggest that wall thickness was structurally adapted to keep w/ri balanced to the prevailing blood pressure, while internal radius was adapted to long-term changes in diastolic filling. Thus sympatholytic drugs which lowered arterial pressure by reducing cardiac output, induced a reduction of wall thickness at a minor change of internal radius, while drugs which reduced pressure by systemic vasodilation increased internal radius, thus reducing w/ri. Further, the results stress the importance also to consider the type of load which causes LV hypertrophy, and how rapidly it is imposed. Thus, renal hypertension was associated with reduced LV performance, despite considerable hypertrophy. However, on reversal of renal hypertension by unclipping, cardiac function was soon enhanced to match the degree of LV hypertrophy as in SHR. This suggests that the renal hypertensive state per se adds some cardio-depressive influence, possibly by inducing reversible changes of cardiac myosin isoenzymes, which tends to offset the improved ventricular performance inherent in LV hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structural and functional adaptation in the rat myocardium and coronary vascular bed caused by changes in pressure and volume load. 316 Dec 69

Reports from several laboratories indicate that the early part of smooth muscle contraction is achieved by normally cycling crossbridges, while the later part is subserved by slowly cycling or latch-bridges. We have recently found that the early bridges are responsible for almost 75% of the maximum shortening of the muscle. The latch bridges appear to be responsible for force production. The earliest change in the mechanical properties of caudal arteries from spontaneously hypertensive rats (SHR) is an increase in maximum shortening ability (delta Lmax), at a time when there is no detectable change in maximal isometric tetanic tension (Po). This substantiates the hypothesis that changes in Po are late indices of disease. The increased delta Lmax is associated with increased maximal velocity of shortening (Vo) of early cross-bridges, whereas latch bridge activity is normal. This provides the first subcellular explanation for the increase in delta Lmax. Since hypertension must result from narrowing of blood vessels, delta Lmax is, parenthetically, the important variable to study. Changes in Po, while contributing to increased vascular wall stiffness, do not directly account for the increased resistance. The cause of the increased cycling rate of crossbridges is probably increased myosin ATPase activity, or myosin light-chain phosphorylation by the specific kinase. Studies in helical sections of caudal, and segments of mesenteric resistance arteries provided similar results, confirming the suitability of caudal arteries as a model of resistance vascular units. The larger vessel is of course much easier to work with.
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PMID:Mechanical properties of vascular smooth muscle in hypertension. 332 95

In the spontaneously hypertensive rat (SHR) with established hypertension left ventricular mass closely correlated with the proportion of ventricular myosin (VM)-3. A 60% VM-3 content was reached corresponding, under the present housing conditions, to an average age of 40 weeks without any significant change in total noradrenaline content. However, all 72-week-old SHR showed marked reduction in total noradrenaline content which corresponded to noradrenaline depletion. At this stage, the proportion of VM-3 varied greatly; some of the SHR exhibited a higher proportion of VM-3 than would be expected from their ventricular weight. The excessive redistribution in the direction of VM-3 might, therefore, be considered as a reaction secondary to noradrenaline depletion. Total dopamine content was also reduced in 72-week-old SHR. In younger SHR, a positive correlation was found for dopamine content and left ventricular weight. It is concluded that a redistribution of the myosin isoenzymes up to 60% VM-3 in SHR is not associated with deterioration of ventricular performance to the extent that an excessive neurohumoral drive ensues. However, in the late stage of haemodynamic overload, a functional state is reached which is prone to noradrenaline depletion. A causative factor involved in this process could be the extreme redistribution of the myosin isoenzyme population, besides other factors such as fibrosis and dilatation. Which functional determinants or structural elements are finally decisive for the transition into a myocardium with depleted noradrenaline stores requires further investigation.
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PMID:Correlation between total catecholamine content and redistribution of myosin isoenzymes in pressure loaded ventricular myocardium of the spontaneously hypertensive rat. 379 40

Vascular stiffening and a modest increase in cardiac mass with advancing age in man resemble similar alterations accompanying chronic arterial hypertension. In both hypertensive and elderly normotensive individuals, systolic pump function at rest is not altered, while early filling rate and volume are decreased. Although this abnormality is often attributed to the cardiac hypertrophy per se, prolonged isometric relaxation, which occurs with aging in man and animals and in some types of experimental hypertension, is an equally plausible mechanism. In the aged rat, prolonged relaxation can be attributed to a prolonged myoplasmic Ca++ transient with excitation. This occurs amidst a constellation of other cellular changes, among which are a markedly prolonged transmembrane action potential, diminished sarcoplasmic reticulum Ca++ pumping rate, and altered myosin isozyme composition. Many of these changes occur in cardiac muscle of younger animals with cardiac hypertrophy due to chronic increased afterload. While the magnitude of these alterations with advanced age is as great as those with chronic hypertension in younger animals, the magnitude of left ventricular hypertrophy with aging is far less than that in experimental hypertension. Furthermore, with aging, these alterations occur not only in the myocardium of the left but also of the right heart (which does not hypertrophy). Thus, myocardial hypertrophy per se does not appear to be the common link between cellular changes due to aging and those due to hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Do hypertension and aging have a similar effect on the myocardium? 379 21

The aim of this study was to clarify whether the increased vascular tone in spontaneous hypertension of rats is due to a change of the calcium-sensitivity of the contractile proteins themselves. In skinned rat tail artery rings from SHRSP and WKY rats the calcium-requirement for half maximal activation (3.6 X 10(-6)M Ca++ for both rat strains) as well as relaxation half times (1.45 +/- 0.43 min, SHRSP and 1.63 +/- 0.48 min, WKY) were found to be identical. The extent of myosin phosphorylation in the contracted and in the relaxed state did not differ between SHRSP and WKY. It is concluded that changes at the level of the contractile proteins are not involved in the increased vascular tone of SHRSP essential hypertension.
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PMID:Calcium-requirement for activation of skinned vascular smooth muscle from spontaneously hypertensive (SHRSP) and normotensive control rats. 394 63

Pressure-overload cardiac hypertrophy and hypothyroidism were shown to be associated with a decreased maximum shortening velocity of the myocardium. To investigate the nature of these intrinsic myocardial changes, we studied the energetic consequences in left ventricular papillary muscles of the rat by using standard HILL planar vacuum-deposited antimony-bismuth thermopiles. To evaluate the economy of isometric force generation and maintenance, we analyzed the ratio of liberated heat and developed tension or developed tension-time integral in twitches and experimentally induced tetanic contractions. Hypothyroidism was induced by treatment with propylthiouracil (PTU), and hypertension by operative narrowing of the left renal artery of rats according to Goldblatt (GOP). In the myocardium of hypothyroid as well as hypertensive rats, initial heat per peak twitch tension and total activity-related heat per tension-time integral were significantly reduced compared to controls. In tetanic contractions, total activity-related heat per tension-time integral was also decreased in PTU and GOP myocardium when compared to controls. Thus, the economy of force generation and maintenance is improved in the myocardium of the experimental animals. The data is interpreted in terms of altered cross-bridge cycling rates which are shown to be associated with changes in the myosin isoenzyme pattern. The intrinsic changes of the myocardium due to pressure-overload hypertrophy and hypothyroidism are considered to be adaptive rather than pathologic reactions of the myocardium.
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PMID:Energetic changes of myocardium as an adaptation to chronic hemodynamic overload and thyroid gland activity. 409 75

Hypertension and resulting left ventricular hypertrophy was induced in young male Wistar rats (60 to 70 days old) by narrowing of one renal artery (Goldblatt II). 8 and 24 weeks after operation, myocardial oxygen consumption was measured on a modified in situ heart-lung preparation with nearly isovolumetric left ventricular contractions. Measured myocardial oxygen consumption was related to left ventricular wall stress. The myosin isoenzyme pattern of each heart was determined with pyrophosphate gel electrophoresis. Oxygen consumption related to wall stress averaged over the entire heart cycle amounted to 15 mumoles O2/g X min 8 weeks after operation, and 24.4 mumoles O2/g X min in age-matched controls (delta 38%, p less than 0.0005). When wall stress was averaged over systole, oxygen consumption of the hypertrophied hearts amounted to 0.112 mumoles O2/g x beat, and 0.149 mumoles O2/g x beat in the controls (delta 25%, p less than 0.05). The proportion of VM-3 (the cardiac myosin isoenzyme of lowest ATPase activity) increased from 26.3% in the controls to 30.1% in the Goldblatt hearts (delta 14%, n.s.). 24 weeks after operation, oxygen consumption related to wall stress averaged over the entire heart cycle amounted to 16.1 mumoles O2/g x min, in age-matched controls 20.5 mumoles O2/g x min (delta 21%, p less than 0.05). When wall stress was averaged over systole, oxygen consumption of the Goldblatt hearts amounted to 0.080 mumoles O2/g x beat, and in the controls 0.107 mumoles O2/g x beat (delta 25%, p less than 0.0005). The proportion of VM-3 increased from 33.5% in the controls to 43.2% in the hypertrophied hearts (delta 29%, p less than 0.05). The present findings indicate that the reduced oxygen consumption of the pressure-loaded heart should be attributed to a redistribution of myosin isoenzymes. The transformation of myocardium into a slower, but more efficiently working muscle due to an increase in VM-3 can be interpreted as an adaptational process.
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PMID:Alterations in cardiac oxygen consumption under chronic pressure overload. Significance of the isoenzyme pattern of myosin. 621 50

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


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