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At least 1,063 records · Page 59Linked to original sources
PubMed2005

Myocardial fibrosis, impaired coronary hemodynamics, and biventricular dysfunction in salt-loaded SHR.

Arterial pressure in most experimental and clinical hypertensions is exacerbated by salt. The effects of salt excess on right and left ventricular (RV and LV, respectively) functions and their respective coronary vasodilatory responses have been less explored. We therefore examined the effects of 8 wk of NaCl excess (8% in food) on arterial pressure, RV and LV functions (maximal rate of increase and decrease of ventricular pressure; dP/dt(max) and dP/dt(min)), coronary hemodynamics (microspheres), and collagen content (hydroxyproline assay and collagen volume fraction) in young adult normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), aged 16 wk by the end of the study. Prolonged salt excess in WKY and SHR elevated pressure only modestly, but it markedly increased LV mass, especially in SHR. Moreover, salt excess significantly impaired RV and LV diastolic function in SHR but only LV diastolic function in WKY rats. However, salt loading affected neither RV nor LV contractile function in both strains. Interstitial and perivascular collagen deposition was increased, whereas coronary vasodilatory responses to dipyridamole diminished in both ventricles in the salt-loaded SHR but not in WKY rats. Therefore, accumulation of ventricular collagen as well as altered myocardial perfusion importantly contributed to the development of salt-related RV and LV dysfunctions in this model of naturally occurring hypertension. The unique effects of salt loading on both ventricles in SHR, but not WKY rats, strongly suggest that nonhemodynamic mechanisms in hypertensive disease participate pathophysiologically with salt-loading hypertension. These findings point to the conclusion that the concept of "salt sensitivity" in hypertension is far more complex than simply its effects on arterial pressure or the LV.

Animals↗
PubMed1995

Role of angiotensin II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover.

In hypertensive heart disease, after myocardial infarction or in congestive heart failure, myocardial fibrosis presenting as a diffuse perivascular and interstitial accumulation of fibrillar collagens within the normal connective tissue structures of the myocardium is associated with an activated renin-angiotensin system (RAS). This reactive fibrosis occurs in the overloaded left ventricle and the nonoverloaded right ventricle irrespective of myocyte necrosis or the development of myocyte hypertrophy. Therefore, it appears that hemodynamic factors or the load of the ventricle are not primarily responsible for the adverse fibrous tissue response in the myocardium, and humoral factors may play a key role in regulating the myocardial collagen matrix. The neurohumoral response in hypertensive heart disease, after myocardial infarction with overall deterioration of left ventricular function or congestive heart failure leads to an activation of either the cardiac or the circulating RAS, which closely interacts with the bradykinin-prostaglandin system. To ascertain whether the RAS modulates collagen fibroblasts that express mRNAs for types I and III collagens (the major fibrillar collagens in the heart) and matrix metalloproteinase 1 (MMP1; the key enzyme for collagen degradation), collagen synthesis was measured by [3H]proline incorporation normalized to total protein synthesis and MMP1 activity was determined by degradation of [14C]collagen in cultured fibroblasts after 24-hour incubation with various concentrations of angiotensin II or PGE2 (10(-11)-10(-3) M) under serum-free conditions. In addition, effects of angiotensin II were evaluated in the presence or absence of either type 1 (ICI D8731) or type 2 (PD 123177) angiotensin II (AT1 or PGE2 (10(-11)-10(-3) M) under serum-free conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Angiotensin II stimulates the autocrine production of transforming growth factor-beta 1 in adult rat cardiac fibroblasts.

Angiotensin II (Ang II) has been implicated in the development of cardiac hypertrophy and myocardial fibrosis. While recent in vivo and in vitro studies performed in cultured cardiac myocytes and fibroblasts support this role for Ang II, the mechanisms of Ang II action at the cellular level remain unclear. In the present study, we postulated that Ang II action in adult cardiac fibroblasts may stimulate the autocrine production and release of transforming growth factor-beta 1 (TGF-beta 1), a known regulator of cardiac fibroblast and myocyte function. We examined the ability of Ang II to regulate the gene expression, biological activity, and protein production of TGF-beta 1 in cultured adult rat cardiac fibroblasts. Treatment of fibroblast cultures with Ang II (10(-9) M) induced a two-fold increase in TGF-beta 1 mRNA levels within 4 h that was sustained through 24 h (P < 0.01). TGF-beta 1-like activity in Ang II-treated cultures was significantly increased compared with control as measured by bioassay (P < 0.001). Specificity for TGF-beta 1-like activity was confirmed through its neutralization with a TGF-beta 1 specific antibody (100 micrograms/ml). Total concentration of TGF-beta 1 (latent plus active forms) in conditioned media from Ang II-treated cardiac fibroblasts was also found to be greater than control (P < 0.01). These findings suggest that the effects of Ang II in the adult myocardium may be mediated in part by autocrine/paracrine mechanisms, including the production and release of TGF-beta 1 by cardiac fibroblasts.

Angiotensin II↗
PubMed2006

Role of aldosterone in left ventricular hypertrophy in hypertension.

BACKGROUND: Aldosterone induces cardiac fibrosis in experimental animal models, but only limited information is available on the association between aldosterone and left ventricular (LV) hypertrophy in human beings. The aim of the present study was to determine the role of aldosterone in LV geometry and to investigate other types of target organ damage in hypertensive patients. METHODS: A total of 25 patients with primary aldosteronism caused by Conn's adenoma, 29 patients with renovascular hypertension, and 29 patients with essential hypertension (EHT) were included in the present study. Echocardiographic examinations and 24-h ambulatory blood pressure (BP) monitoring were conducted in all subjects. RESULTS: The mean 24-h systolic and diastolic BP in primary aldosteronism and renovascular hypertension were found to be comparable to those in EHT. However, LV mass index adjusted by age, sex, mean 24-h systolic BP, mean 24-h pulse rate, body mass index, and duration of hypertension was significantly increased in the patients with primary aldosteronism and renovascular hypertension compared with values in patients with EHT (150.2 +/- 7.7, 142.3 +/- 7.2, and 115.2 +/- 7.2 g/m(2), respectively). Hypertensive organ damages, such as proteinuria and hypertensive retinopathy, were more pronounced in the patients with renovascular hypertension; however, LV hypertrophy was especially exaggerated in patients with primary aldosteronism. CONCLUSIONS: These results indicate that aldosterone may induce LV hypertrophy in human beings as well as in experimental animals, and that angiotensin II and aldosterone may differentially participate in causing hypertensive target organ damage.

Adrenergic beta-Antagonists↗
PubMed1992

Effect of captopril on the prevention and regression of myocardial cell hypertrophy and interstitial fibrosis in pressure overload cardiac hypertrophy.

This article reports on the effects of captopril on both the prevention and the regression of myocardial cell hypertrophy and interstitial fibrosis in experimental animals (rats) with pressure overloaded hearts. Constriction of the abdominal aorta just below the diaphragm during periods of 20 days (prevention experiment) and 40 days (regression experiment) resulted in hypertension and cardiac hypertrophy. In the prevention experiment, captopril was able to inhibit the development of high blood pressure levels and cardiac hypertrophy in aortic-constricted rats. Similarly, the treatment of sham-operated rats with captopril led to a reduction in the weight of the heart and in the myocyte diameter compared with controls. The myocyte volume fraction of the left ventricles of both aortic-constricted and sham-operated animals that were treated with captopril was significantly diminished compared with that of the control group. The interstitial collagen volume fraction of all experimental groups was elevated as compared with the control group. As a consequence, the ratios of myocytes to interstitial collagen in groups of aortic-constricted rats, aortic-constricted rats that were treated with captopril, and sham-operated rats that were treated with captopril were reduced compared with the control group; that is, although captopril was able to prevent myocardial cell hypertrophy after aortic constriction, it could not prevent the maintenance of a normal ratio of myocytes to interstitial collagen, which was due to increased collagen volume fraction. In the regression experiment, captopril lowered high blood pressure levels and augmented heart weights to control values. The mean myocyte transverse diameter in aortic-constricted rats that were treated with captopril was significantly smaller than that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

F110I and R278C troponin T mutations that cause familial hypertrophic cardiomyopathy affect muscle contraction in transgenic mice and reconstituted human cardiac fibers.

We have studied the physiological effects of the troponin T (TnT) F110I and R278C mutations associated with familial hypertrophic cardiomyopathy (FHC) in humans. Three to four-month-old transgenic (Tg) mice expressing F110I-TnT and R278C-TnT did not develop significant hypertrophy or ventricular fibrosis even after chronic exercise challenge. The F110I mutation impaired acute exercise tolerance, whereas R278C did not. Skinned papillary muscle fibers from transgenic mice expressing F110I-TnT demonstrated increased Ca(2+) sensitivity of force and ATPase activity, and likewise an increased Ca(2+) sensitivity of force was observed in F110I-TnT-reconstituted human cardiac muscle preparations. In contrast, no changes in force or the ATPase-pCa dependencies were observed in transgenic R278C fibers or in human fibers reconstituted with the R278C-TnT mutant. The maximal level of force development was dramatically decreased in both transgenic mice. However, the maximal ATPase was not different (R278C-TnT) or only slightly less (F110I-TnT) than that of non-Tg and WT-Tg littermates. Consequently, their ratios of ATPase/force (energy cost) at all Ca(2+) concentrations were dramatically higher compared with non-Tg and WT-Tg fibers. This increase in energy cost most likely results from a decrease in force per myosin cross-bridge, because forcing all cross-bridges into the force generating state by substitution of MgADP for MgATP in maximum contracting solutions resulted in the same increase in maximal force (15%) in all transgenic and non-transgenic preparations. The combination of increased Ca(2+) sensitivity and energy cost in the F110I hearts may be responsible for the greater severity of this phenotype compared with the R278C mutation.

Adenosine Triphosphatases↗
PubMed1996

Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.

In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After perfusion fixation, heart and aorta were examined by stereological techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Age-dependent expression of fibrosis-related genes and collagen deposition in the rat myocardium.

OBJECTIVES: We sought to characterize the evolution, during maturational growth and early ageing, of the messenger abundance of four genes involved in cardiac fibrosis regulation (procollagens alpha2(I) and alpha1(III), transforming growth factors beta1, and beta3) and corroborate it with the alterations in collagen deposition in cardiac interstitium and around coronary arteries. METHODS: Messenger RNA was quantified in LV and RV of 2-, 6-, 12- and 19-month-old male Sprague-Dawley rats (n = 5 per group) with Northern blot analysis. Collagen deposition was quantified with a semi-automated image analyser on Sirius red-stained sections of LV tissue. RESULTS: There was an age-related monotonous decrease of procollagen type I (COL-I) transcript abundance in LV (p < 0.001) but not in RV. Procollagen type III (COL-III) expression decreased rapidly during maturational growth, both in LV and RV. On the other hand, collagen deposition in myocardial interstitium and around coronary arteries was slightly augmented during the maturational period of life (2-12 months), but with a higher rate during early ageing (up to 19 months). This was not accompanied by a significant thickening of the wall of coronary arteries. Transforming growth factor beta1, (TGF-beta1) and transforming growth factor beta3 (TGF-beta3) transcript abundance showed no major variations during ageing. CONCLUSIONS: These results reflect a striking ventricular difference regarding the age-dependent expression of COL-I. The expression of TGF-beta(s), pleiotropic factors known to influence collagen pathway at different levels, does not seem to be profoundly altered during ageing. The discrepancy between protein and COL-I and COL-III mRNA levels indicates differences in age-related mRNA stability and/or regulation of collagen translation.

Aging↗
PubMed1998

Angiotensin converting enzyme inhibition modulates cardiac fibroblast growth.

BACKGROUND: The progression of left ventricular hypertrophy and cardiac fibrosis in hypertensive heart disease is influenced by sex and age. Although angiotensin converting enzyme inhibition has been shown to prevent progression of the disease in postmenopausal women, the interaction of angiotensin II and estrogen in this process before and after the menopause is poorly understood. OBJECTIVE: To investigate the influence of the angiotensin converting enzyme inhibitor moexiprilat on serum, estrogen and angiotensin II-induced cardiac fibroblast growth. METHODS: Neonatal rat cardiac fibroblasts were incubated with 1 and 10% fetal calf serum, 10(-7) mol/l angiotensin II, 10(-9) mol/l estrone, 10(-9) mol/l 17beta-estradiol and 10(-8) mol/l moexiprilat. Proliferation was measured in terms of incorporation of bromodeoxyuridine. Western blot analysis was performed using antibodies directed against the growth-related immediate early genes c-fos and Sp-1. All experiments were performed at least three times. RESULTS: Fetal calf serum stimulated cardiac fibroblast proliferation (1% fetal calf serum 2.0+/-0.028-fold; 10% fetal calf serum 2.7+/-0.028-fold). Angiotensin II and estrone stimulated proliferation of cardiac fibroblasts grown in the absence of fetal calf serum (angiotensin II 4.2+/-0.075-fold; estrone 2.9+/-0.034-fold) and further increased proliferation in the presence of 1% fetal calf serum (angiotensin 11 4.3+/-0.072-fold); estrone 3.8+/-0.045-fold) and 10% fetal calf serum (angiotensin II 4.8+/-0.112-fold; estrone 4.1+/-0.047-fold). Coincubation with moexiprilat specifically inhibited proliferation induced by angiotensin II and estrone but not by serum, and angiotensin II type 1 receptor blockade inhibited angiotensin II-induced but not estrone-induced cell growth. Western blot analysis showed that the expression of c-fos and Sp-1 was induced in a time-dependent fashion by angiotensin II (to maxima of 5.0-fold for c-fos and 3.0-fold for Sp-1) and estrone (15.2-fold for c-fos and 6.2-fold for Sp-1). This effect was completely inhibited by moexiprilat. CONCLUSIONS: Angiotensin converting enzyme inhibition modulates cardiac fibroblast growth induced by angiotensin II and estrone. This mechanism might contribute to the beneficial effects of angiotensin converting enzyme inhibition in postmenopausal patients with hypertensive heart disease.

Angiotensin II↗
PubMed1979

Polyarteritis nodosa in childhood a clinical pathologic study.

The clinical and pathologic findings of 2 infants and 7 older children with polyarteritis nodosa who were autopsied are reported. The most frequent clinical features included prolonged high fever, skin rash, abdominal symptoms, leukocytosis, proteinuria, and signs of either cardiac or renal failure. The 2 infants died of cardiac arrest, whereas renal or neurologic involvement was the most common cause of death in the older children. A consistent finding at autopsy was arteritis of the epicardial coronary arteries.

Adolescent↗
PubMed1985

Endomyocardial biopsy: a review of the literature.

A review of the literature relating to endomyocardial biopsy (EMB) is presented. This is considered important at this time since EMB is being utilized with increasing frequency, particularly for the diagnosis of myocarditis. The development of the technique is briefly outlined. Emphasis is placed on the clinical application of EMB in the various primary cardiomyopathies (dilated, hypertrophic, restrictive, and obliterative), the infiltrative secondary cardiomyopathies (amyloidosis, sarcoidosis, hemochromatosis), myocarditis, as well as such conditions as adriamycin cardiotoxicity, cardiac transplant rejection, and Kawasaki disease. More controversial application of EMB in primary mitral valve prolapse (Barlow's syndrome), idiopathic ventricular arrhythmias, and the elucidation of the enigmatic finding of angina with angiographically normal coronary arteries is detailed. Experience with immunological and biochemical investigation of biopsy material, as well as with virus isolation and drug assays in the myocardium, is alluded to. Complications encountered with this procedure are also discussed, and its future role is contemplated.

Amyloidosis↗
PubMed1986

Eosinophilic endomyocardiopathy.

A young patient with a severely elevated eosinophil count died from manifestations of severe eosinophilic endomyocardiopathy. Echocardiographic and hemodynamic evaluation were diagnostic of a rapidly progressive restrictive cardiomyopathy. Progression of cardiac disease in the face of medical treatment is an ominous sign and may argue for earlier surgical intervention in this syndrome.

Adult↗
PubMed1991

Electromechanical concordance in alternans during sustained tachycardias.

Electrical alternans and mechanical alternans are intriguing phenomena that have been reported to occur during tachycardias. Their precise pathophysiologic mechanism and in particular their interrelation have not been well defined. This report documents an unusual electromechanical concordance in alternans during sustained supraventricular tachycardia and ventricular tachycardia in two patients, raising interesting possibilities on the underlying mechanism of the concordant phenomena. The findings highlight the principle of excitation--contraction coupling of the heart.

Adult↗
PubMed1991

Laser-induced fluorescence emission: I. The spectroscopic identification of fibrotic endocardium and myocardium.

UNLABELLED: Laser-induced fluorescence has been developed as a guidance system for laser angioplasty. Laser ablation has been used for resection of arrhythmogenic ventricular scar. We have investigated the use of laser-induced fluorescence for the detection of fibrotic and ischemic changes in endocardium and myocardium. Fluorescence emission spectra from human necropsy specimens were correlated with histologic examination. Normalized fluorescence intensity detected from both the endocardial and the myocardial surfaces of the fibrotic ventricular specimens was significantly higher than that of corresponding normal specimens at 440 to 475 nm. Fibrotic endocardium could be identified by a fluorescence emission intensity ratio less than 1.5 for wavelength ratio 375/450nm. Acutely infarcted endocardium was recognizable by a ratio of 1.5 to 2.0. The specificity and sensitivity of detection of scarred endocardium was 70 and 100%, respectively. Fibrotic myocardium was also consistently identified by fluorescence spectroscopy. CONCLUSION: Fluorescence emission spectroscopy can differentiate normal and fibrotic endocardium and myocardium, in vitro. This technique may be useful for guidance during laser ablation of arrhythmogenic ventricular scar.

Capillaries↗
PubMed1979

Aortic body tumours and hyperplasia in the rat.

The histologic features of aortic body neoplasia, hyperplasia, and normal aortico-pulmonary paraganglia were described for a series of 56 rats of several strains. Argyrophilic cytoplasmic granules were demonstrated in chief cells of the aortic body lesions, and electron microscopic examination disclosed the presence of electron-dense, membrane-bound granules in these cells. In a series of ageing rats, hyperplasia and neoplasia of the aortico-pulmonary paraganglia occurred more frequently in female WAG/Rij rats than in males of that strain, and more frequently than in males and females of the BN/Bi strain or of the (WAG X BN)F1 hybrid. No apparent causal relationship to chronic hypoxia could be shown, in that no correlation between the development of aortic body neoplasia or hyperplasia and cardiopulmonary disease was found. Aortic body lesions did not appear to occur as part of a multiple endocrinopathy syndrome, although hyperplasia and neoplasia of various endocrine organs occurred relatively frequently in the WAG/Rij strain.

Aging↗
PubMed1993

Myocardial collagen and its functional role.

Even though normally present in relatively small amounts, myocardial collagen strongly influences ventricular diastolic function. Removal of less than half of the normal amount results in a dilated ventricle with increased compliance. In contrast, an abnormal increase in collagen concentration results in a stiffer myocardium and ventricular diastolic dysfunction.

Animals↗
PubMed1993

Current therapy of systemic sclerosis (scleroderma).

Treatment of systemic sclerosis (scleroderma) presents a challenge to both the patient and the physician. Established approaches include long-term physiotherapy, disease-modifying agents such as D-penicillamine, and treatment of organ involvement. These efforts are often unsatisfactory since the results are poor. However, recent advances include treatment of Raynaud's phenomenon (plasmapheresis, stanozolol, and prostacyclin analogues), scleroderma renal crisis (angiotensin-converting enzyme inhibitors), and gastric hypomotility (cisapride). This article covers the current approaches to the disease-modifying therapy including those related to the function of collagen-producing fibroblasts, vascular alterations, and the cellular and humoral immune system, as well as treatment of involved organs.

Acute Kidney Injury↗