Alterations in cardiac SR Ca²⁺-release channels during development of heart failure in cardiomyopathic hamsters

Abstract

The cardiomyopathic Syrian hamster develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, cardiac dilatation, and congestive heart failure. This study aimed to identify alterations in cardiac mechanical function and in the cellular content of sarcoplasmic reticulum (SR) Ca2+-release channels (ryanodine receptors, RyR) in the heart of the UM-X7.1 cardiomyopathic hamster during the development of heart failure. Experimental and healthy control hamsters were examined at 8, 18, and 28 wk of age. The UM-X7.1 hamsters had developed left ventricular (LV) hypertrophy at 8 wk and a marked LV dilatation at 18–28 wk. During the latter stage, the UM-X7.1 hamster hearts showed global hypokinesis. Equilibrium binding assays of high-affinity sites for [3H]ryanodine were performed in ventricular homogenate preparations. There was no significant difference between the two groups in the maximum number of [3H]ryanodine binding sites (Bmax) at either 8 or 18 wk of age, although the cardiac pump function was impaired in UM-X7.1 hamsters at 18 wk of age. By 28 wk, Bmax was significantly lower in the UM-X7.1 hamsters. Quantitative immunoblot assay revealed that the content of RyR protein in cardiomyopathic hearts, which was increased at the early stage, declined to below normal as heart failure advanced. These results suggest that the number of RyR in the UM-X7.1 cardiomyopathic hamsters was preserved at both the hypertrophic and early stages of heart failure with a possibly compensatory increase in the level of protein expression, although the cardiac function already showed a tendency to be impaired.

Beneficial Effects of the Dual L- and T-Type Ca2+ Channel Blocker Efonidipine on Cardiomyopathic Hamsters

“…Our choice of this dose and timing of administration of EFO was based on a pilot study in which the results showed that the serum level of EFO significantly increased without producing a significant decrease in blood pressure in the hamsters. Also, according to our previous report, 7 cardiac function in the UM-X7.1 hamster is impaired at the age of 18-20 weeks. The care of the animals and the protocols conformed with the Guiding Principles in the Care and Use of Animals and were in accord with guidelines laid down by the Animal Ethics Committee of Yamaguchi University Graduate School of Medicine.…”

“…To enable us to determine the left ventricular (LV) dimensions and assess the contractile state in vivo, transthoracic echocardiography was performed as previously described 7 (echocardiograph model SSD-1000, Aloka, Tokyo, Japan, with a 10-MHz sector scan probe). After the echocardiographic examination was completed, the hamsters were given additional pentobarbital sodium (30 mg/kg, im) and the chest was quickly opened.…”

“…Immunoblot analysis was performed as previously described, 7 with some modifications. The membrane protein (50 g protein/lane) was electrophoresed on 6% SDS-polyacrylamide gels.…”

Lesions in Ryanodine Channels in Smooth Muscle Cells Exposed to Oxidized Low Density Lipoprotein

“…Alterations in the function or content of these proteins have been suggested to contribute to contractile dysfunction in muscle cells during many different disease processes. 31,32 Our data demonstrate that the ryanodine-sensitive channels are depressed in vivo in aortic sections of atherosclerotic plaque in cholesterol-fed rabbits. This depression is particularly evident within and under the plaque area, suggesting that a component associated with the atherogenic environment induces this lesion.…”

Effects of Cardioplegic Arrest and Reperfusion on Rabbit Cardiac Ryanodine Receptors

“…17,18 Briefly, the microsomal fraction that was rich in SR vesicles (0.4 mg/ml) was incubated for 90 min at 37°C in 25 mmol/L imidasole (pH 7. , then removed while under vacuum. After the addition of 5 ml of scintillation fluid, the radioactivity was counted in a scintillation counter (LSC-5100; Aloka, Tokyo, Japan).…”