6-ketoprostaglandin-f1-alpha and Cardiomyopathy--Dilated

The aim of the present work was to analyze coronary endothelial function in the transgenic mouse model of dilated cardiomyopathy (Tgalphaq*44 mice).. Coronary vasodilatation, both NO-dependent (induced by bradykinin) and PGI(2)-dependent (induced by acetylcholine), was assessed in the isolated hearts of Tgalphaq*44 and FVB mice. Cardiac function was analyzed in vivo (MRI).. In Tgalphaq*44 mice at the age of 2-4 months cardiac function was preserved and there were no alterations in endothelial function. By contrast, in Tgalphaq*44 mice at the age of 14-16 months cardiac function was significantly impaired and NO, but not PGI(2)-dependent coronary function was altered. Interestingly, the basal level of PGI(2) in coronary circulation increased fourfold as compared to FVB mice. Cardiac O(2) (-) production increased 1.5-fold and 3-fold in Tgalphaq*44 vs. FVB mice at the age of 2-6 and 14-16 months, respectively, and was inhibited by apocynin. Interestingly, inhibition of NADPH oxidase or NOS-3 normalized augmented PGI(2) production in Tgalphaq*44 mice. There was also an increased expression of gp91phox in Tgalphaq*44 vs. FVB hearts, without evident alterations in the expression of COX-1, COX-2, NOS-3 and PGI(2)-synthase.. In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI(2). Both the decrease in NO activity and the increase in PGI(2) activity may result from excessive O(2) (-) production by cardiac NADPH oxidase in Tgalphaq*44 hearts.

Topics: 6-Ketoprostaglandin F1 alpha; Age Factors; Animals; Cardiomyopathy, Dilated; Coronary Artery Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cytochrome P-450 Enzyme System; Disease Models, Animal; Endothelium, Vascular; Epoprostenol; Heart Failure; Intramolecular Oxidoreductases; Membrane Proteins; Mice; Mice, Inbred Strains; Mice, Transgenic; Myocardium; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Superoxides; Vasodilation

We demonstrated that the activities of phosphatidylinositide-specific phospholipase C, inositol 1,4,5-trisphosphate (IP3) kinase, and IP3 phosphatase were enhanced in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) in comparison to control hamsters (F1b). Release of both arachidonic acid and prostacyclin was markedly enhanced by norepinephrine in the cardiomyopathic hamsters. Phospholipase C in heart has high substrate specificity to phosphatidylinositol. IP3 production was markedly enhanced in the cardiomyopathic hamsters. We also determined the intracellular calcium concentration, which was higher in BIO 53.58 hamsters than in BIO 14.6 hamsters at 5-20 weeks of age. There was no significant difference in the intracellular calcium level between F1b and BIO 14.6 hamsters at 5 weeks of age. These results suggest that phosphatidylinositol turnover stimulated by norepinephrine may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in BIO 53.58 hamsters, some mechanism such as the sarcoplasmic reticulum, which controls the intracellular calcium level, may deteriorate in function. We concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Catalysis; Cricetinae; Enzyme Activation; Male; Mesocricetus; Norepinephrine; Phosphatidylinositols; Phospholipids; Type C Phospholipases

The changes in 12 parameters of hemorheology were observed and the levels of peripheral plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) measured in 35 cases of dilated cardiomyopathy (DCM), including 6 peripartum cardiomyopathy (PCM). We found that there is of hyperviscosity in DCM, the causes were decrease of erythrocyte deformability, increase of red blood cell aggregation, increase of plasma fibrinogen and TXA2 level and decrease of plasma 6-keto-PGF1 alpha level.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Blood Viscosity; Cardiomyopathy, Dilated; Erythrocyte Aggregation; Erythrocyte Deformability; Female; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboxane B2