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Abstract

The hyperglycaemia and oxidative stress, that occur in diabetes mellitus, cause impairment of membrane functions in cardiomyocytes. Also reduced sensitivity to Ca-overload was reported in diabetic hearts (D). This enhanced calcium resistance is based on remodelling of the sarcolemmal membranes (SL) with down-regulated, but from the point of view of kinetics relatively well preserved Na,K-ATPase and abnormal Mg- and Ca-ATPase (Mg/Ca-ATPase) activities. It was hypothesised that in these changes may also participate the non-enzymatic glycation of proteins (NEG) and the related free radical formation (FRF), that decrease the membrane fluidity (SLMF), which is in reversal relationship to the fluorescence anisotropy (D 0.235 +/- 0.022; controls (C) 0.185 +/- 0.009; p < 0.001). In order to check the true role of SLMF in hearts of the diabetic rats (streptozotocin, single dose, 45 mg/kg i.v.) animals were treated in a special regimen with resorcylidene aminoguanidine (RAG 4 mg/kg i.m.). The treatment with RAG eliminated completely the diabetes-induced decrease in the SLMF (C 0.185 +/- 0.009; D + RAG 0.167 +/- 0.013; p < 0.001) as well as in NEG (fructosamine microg x mg(-1) of protein: C 2.68 +/- 0.14; D 4.48 +/- 0.85; D + RAG 2.57 +/- 0.14; p < 0.001), and FRF in the SL (malondialdehyde: C 5.3 +/- 0.3; D 8.63 +/- 0.2; D + RAG 5.61 +/- 0.53 micromol x g(-1); p < 0.05). Nevertheless, the SL ATPase activity in diabetic animals was not considerably influenced by RAG (increase in D + RAG vs. D 3.3%, p > 0.05). On the other hand, RAG increased considerably the vulnerability of the diabetic heart to overload with external Ca2+ (C 100% of hearts failed, D 83.3%, D + RAG 46.7% of hearts survived). So we may conclude, that: (i) The NEG and FRF caused alterations in SLMF, that accompanied the diabetes-induced remodelling of SL, also seem to participate in the protection of diabetic heart against Ca2+-overload; (ii) Although, the changes in SLMF were shown to influence considerably the ATPase activities in cells of diverse tissues, they seem to be little responsible for changes in ATPases-mediated processes in the SL of chronic diabetic hearts.

Rhythmoinotropic Myocardial Reactions in Rats with Postinfarction Cardiosclerosis against the Background of Streptozotocin-Induced Diabetes

“…Hence, induction of DM against the background of PICS paradoxically preserves the contractile properties of the myocardium. We can hypothesize that glycosylation products increase rigidity of cardiomyocyte membranes; these changes not only decrease activity of enzymes counteracting ischemic damage, but also prevents excessive Ca 2+ entry into the myoplasm [14]. Our results agree with previous reports demonstrating high ischemic resistance of the myocardium (in vivo and in vitro) at early stages of streptozotocin-induced diabetes [3,7].…”

“…D. S. Kondtratieva Diabetes mellitus (DM) aggravates the severity of CHD and increases probability of vascular catastrophes. Among major factors disturbing cardiac function in diabetes mellitus is remodeling of cardiomyocyte membranes by glycosylation and free-radical oxidation end-products [14]. This, in turn, serves as an additional factor of calcium ion imbalance in cardiomyocytes.…”

Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus

“…It is caused to a great extent by change of energy metabolism, which is an additional trigger of functional and structural disorders of heart muscle. In turn, remodeling of the cardiomyocyte membranes with advanced glycation end products and free radical oxidation is essential factor in development of diabetes mellitus [ 5 , 6 ]. All these factors contribute to the disorder of electrical stability of membranes and the ionic balance of heart cells.…”

Diabetes mellitus type 2 and acute myocardial infarction: prognostic options for interaction in patients of different age groups

“…Несмотря на то что клинические результаты свидетельствуют об ухудшении прогноза кардиоваскулярных событий у больных СД, в экспериментальных исследованиях уже с начала 2000 гг. известно парадоксальное повышение устойчивости сердца у животных с СД к повреждающим действиям ишемии и ре- перфузии [12,13]. В ранее опубликованных работах нами также было показано, что при индуцировании СД у крыс через 2 нед после моделирования инфаркта миокарда сократительная функция изолированной папиллярной мышцы сохраняется на уровне интактных животных, при этом уровень кальций-транспортирующих белков саркоплазматического ретикулума (СР) кардиомиоцитов также сопоставим со здоровым миокардом [14].…”

“…Представленные данные позволяют по-новому взглянуть на проблему СД при сердечно-сосудистой патологии, а также на раскрытие механизмов, обусловливающих повышение устойчивости сердца к ишемическим повреждениям. Как известно, все экспериментальные работы, в которых обнаружен эффект кардиопротекции в условиях развития СД, выполнены на условно молодых животных, что соответствует пациентам трудоспособного возраста, представленным 2 группой в настоящем исследовании [12,13,20,21]. Вместе с тем, как оказалось, стареющие крысы Goto-Kakizaki (модель СД2) имеют повышенную чувствительность к ишемиче-ским повреждениям сердца [22].…”