Search

Mechanical forces related to pressure and flow are important for cell hypertrophy and proliferation. We hypothesized the presence of mechanosensors that were solely sensitive to pure atmospheric pressure in the absence of shear and tensile stresses. A pressure-loading apparatus was set up to examine the effects of atmospheric pressure on human aortic smooth muscle cells (HASMC). Pressure application of 140 to 180 mmHg produced DNA synthesis in a pressure-dependent manner. In contrast, pressure of 120 mmHg or less produced no significant change. Pertussis toxin (PTx) completely inhibited the pressure-induced increase of DNA synthesis. Under the high pressure of 200 mmHg. Both extracellular signal-related kinase and c-Jun N-terminal kinase activities, but not p38 activity, were stimulated by pressure of more than 160 mmHg. ACE inhibitor inhibited cell proliferation under the pressure. But the addition of All on ACE inhibitor under the pressure could not recover the cell proliferation.

Recent reports have shown that angiotensin-converting enzyme inhibitors have a role in cardiac remodeling and have beneficial effects on congestive heart failure. But calcium antagonist therapy has been controversial in the treatment of congestive heart failure. The present study examined the effects of the calcium antagonist amlodipine on the morphological changes in the cardiac muscle cells and extracellular matrix and on progressive left ventricular dysfunction in cardiomyopathic hamsters. The effects of amlodipine were compared with enalapril.

Recent reports have shown that angiotensin-converting enzyme inhibitors have a role in cardiac remodeling and have beneficial effects on congestive heart failure. Several studies have described alterations in sarcoplasmic reticulum gene expression in the failing heart. These results indicate that calcium homeostasis in myocytes may be disturbed in congestive heart failure. The present study examines the effects of long-term treatments with the angiotensin-converting enzyme inhibitor Enalapril and Ang II subtype 1 receptor antagonist TCV-116 on the morphological changes in the extracellular matrix, progressive left ventricular dysfunction in cardiomyopathic hamsters. Between age 5–20 weeks, 24 BIO53.58 hamsters (model of dilated cardiomyopathy) received 10mg/kg per day orally either of TCV-116 or no treatment. Between age 5–30 weeks, 24 BIO53.58 hamsters (model of dilated cardiomyopathy) received 20mg/kg per day orally either of Enalapril or no treatment. During the study period, cardiac function was assessed by echocardiography in a noninvasive manner. At 20 or 30 weeks of age, each heart was fixed with 10% formalin, embedded in paraffin, and serial sections were stained with Gomori’s aldehyde fuchsin using the Masson-Goldner method. High framerate ultrasonoscopic echocardiograms revealed that the left ventricular percent fractional shortening (%FS) tended to improve in the Enalapril group (22 ± 4% vs 20 ± 3%) and TCV-116 group (24 ± 4% vs 21 ± 4%). The fibrous tissue volume significantly decreased in Enalapril group (25.2 ± 0.5 mm3, P < 0.05) compared with the untreated group (27.6 ± 2.3mm3). TCV-116 did not significantly decrease the fibrous tissue volume. Enalapril can prevent cardiac remodeling, but TCV-116 is not as effective as Enalapril. Enalapril may nevertheless, suppress fibrosis.

Recently, it has been reported that the signal through the (β-adrenergic signal transduction system in failing heart is reduced. This includes the reduction of (β-adrenergic receptors and Gs-protein, decreased adenylyl activity, and increased Gl-protein (Figure 1). But it is still not clear whether the signal through α-adrenergic receptor changes in failing hearts. From this point of view, we attempted to determine the signal transduction systems in cardiomyopathy using cardiomyopathic hamster hearts. Syrian cardiomyo-pathic hamsters (BIO 14.6 and BIO 53.58) display hereditary abnormalities of the cardiac and skeletal muscles that are inherited as an autosomal recessive trait [1] BIO 14.6 cardiac involvement results in initial myocardial hypertrophy that is followed by cardiac dilatation and death due to congestive heart failure [2]. It is thought that the cardiomyopathic hamster provides a useful model for studying human cardiac diseases, such as hypertrophic cardiomyopathy [3,4].

From the clinical viewpoint, the patients with hypoxaemia have a high incidence of ventricular arrhythmias. However, there have been diverse results in animal models (Turnbull et al., 1965; Szekeres and Papp, 1967; Rogers et al., 1973; Murnaghan, 1975) possibly due to the effects of extracardiac factors such as neurohumoral reflex. To exclude such factors, we used an isolated perfused heart preparation to examine the direct effects of hypoxia on the arrhythmia. In this study, measuring the ventricular fibrillation threshold (VFT) in the isolated perfused rat heart, we examined the oxygen dependence of the susceptibility to ventricular fibrillation quantitatively under various conditions.