lu-208075 and Hypertrophy

Prevalence of major depression in people with chronic heart failure is higher than in normal populations. Depression in heart failure has become a major issue. Psilocybin-containing mushrooms commonly known as magic mushrooms, have been used since ancient times for their mind healing properties. Their safety in cardiovascular disease conditions is not fully known and may pose as a risk for users suffering from these illnesses. Study investigates the effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushrooms use from genus Psilocybe and Panaeolus respectively, in a pathological hypertrophy conditions in which endothelin-1 disorder is a contributor to pathogenesis. We examined the effects of the mushrooms extracts on endothelin-1-induced hypertrophy and tumor necrosis factor-α (TNF- α)-induced cell injury in H9C2 cardiomyocytes. Mushrooms were oven dried and extracted with cold and boiling-hot water. H9C2 cardiomyocytes were induced with endothelin-1 prior to treatment with extracts over 48 h. Cell injury was stimulated with TNF-α. Results proposed that the water extracts of Panaeolus cyanescens and Psilocybe cubensis did not aggravate the pathological hypertrophy induced by endothelin-1 and also protected against the TNF-α-induced injury and cell death in concentrations used. Results support medicinal safe use of mushrooms under controlled conditions and cautioned use of higher concentrations.

Topics: Agaricales; Animals; Endothelin A Receptor Antagonists; Endothelin-1; Hallucinogens; Heart Failure; Humans; Hypertrophy; Myocytes, Cardiac; Phenylpropionates; Psilocybe; Psilocybin; Pyridazines; Rats; Receptor, Endothelin A; Tumor Necrosis Factor-alpha

Compared to the unselective endothelin (ET) receptor antagonist (Bosentan), superior effects of selective ET-A-receptor blockage (Ambrisentan) for the treatment of pulmonary hypertension (PH) are expected due to ET-B-receptor mediated beneficial effects. Our hypothesis was that treatment with Ambrisentan leads to an increase in prostacyclin synthase I (PGIS) expression compared to Bosentan.. To test this hypothesis, rats were treated with either monocrotaline (MCT) only, MCT+Ambrisentan or MCT+Bosentan. After 4 weeks, right ventricular systolic pressure (RVSP), pulmonary vascular remodelling and right ventricular hypertrophy (RV/(LV+S)) were measured.. In MCT only treated animals, significantly greater expression of PGIS mRNA was found in the lungs compared to control animals, and this was confirmed by immunohistochemical analysis indicating increased staining of PGIS in the very small pulmonary arteries (17 % greater expression of PGIS mRNA in MCT versus control, p = 0.002; Remmele score (RS): 51 versus 102, p = 0.009). Treatment with Bosentan resulted in a significantly lower expression of PGIS mRNA compared to Ambrisentan and MCT only (7 % versus 18 %, p = 0.003 and 7 % versus 17 %, p = 0.004). This observation was also confirmed by immunohistochemical analysis (RS very small arteries: 45 versus 81, p = 0.003; RS small arteries: 45 versus 108, p = 0.014). No difference was observed in RVSP, RV/(LV+S) or pulmonary vascular remodelling between the two treatment groups (RVSP: 28 versus 39 mmHg, p = 0.189; RV/(LV+S) 0.46 versus 0.48, p = 0.818; medial area: 78.3 % versus 75.2 %, p = 0.823).. Treatment with Bosentan leads to lower PGIS expression in pulmonary arteries compared to Ambrisentan, although the greater PGIS expression by Ambrisentan treatment had no benefical effect on pulmonary haemodynamics.

Topics: Animals; Bosentan; Cytochrome P-450 Enzyme System; Endothelin Receptor Antagonists; Gene Expression Regulation, Enzymologic; Heart Ventricles; Hemodynamics; Hypertension, Pulmonary; Hypertrophy; Immunohistochemistry; Intramolecular Oxidoreductases; Lung; Male; Organ Size; Phenylpropionates; Pulmonary Artery; Pyridazines; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfonamides