dinoprost and isosorbide-5-mononitrate

Previous studies support a role of oxygen-free radicals in the development of congestive heart failure (CHF). The aim of this study was to investigate whether lipid peroxidation is increased in CHF patients on modern pharmacological therapy and whether there is a positive correlation between plasma levels of markers of lipid peroxidation and severity of heart failure (HF). Plasma malondialdehyde (MDA) and isoprostanes are often used as markers of lipid peroxidation and oxidative stress. We also studied whether long-term treatment with isosorbide-5-mononitrate (IS-5-MN) in combination with standard HF therapy affects P-MDA levels in patients with evidence of left ventricular (LV) dysfunction following acute myocardial infarction (AMI).. Ninety-two patients with clinical or echocardiographic evidence of LV-dysfunction following AMI were randomized to treatment with either IS-5-MN or placebo. In a subgroup of 83 patients with available plasma MDA, echocardiography, right-heart catherization, and plasma natriuretic peptides were evaluated. Control subjects were 80 healthy blood donors. A second study group consisted of 56 patients with CHF, evaluated with respect to LV function, brain natriuretic peptide and markers of oxidative stress (P-MDA and 8-isoprostane). The second control group comprised 50 healthy subjects.. Lipid peroxidation measured by P-MDA and 8-isoprostane was not increased in patients with LV dysfunction treated with standard HF therapy. No positive correlation was found to the severity of HF. Long-term IS-5-MN therapy did not influence P-MDA concentrations.. Although results from many experimental and clinical studies suggest that oxidative stress is increased in HF, this may not be true for patients treated with beta blockers and inhibitors of the renin-angiotensin system.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Captopril; Comorbidity; Delayed-Action Preparations; Dinoprost; Female; Heart Failure; Hemodynamics; Humans; Isosorbide Dinitrate; Lipid Peroxidation; Losartan; Male; Malondialdehyde; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Nitric Oxide Donors; Oxidative Stress; Ramipril; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

The purpose of the study was to investigate possible mechanisms and morphologic changes involved in nitric oxide-induced cervical ripening.. Women scheduled for surgical termination of first trimester pregnancy were randomized to 1 of 3 groups: isosorbide 5-mononitrate 40 mg 4 hours or 10 hours before the operation or no preoperative treatment. Cervical specimens were obtained for the analysis of tissue levels of cyclic guanosine monophosphate, cyclic adenosine monophosphate, cyclo-oxygenase 1, cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) or were fixed in glutaraldehyde for microscopy.. Increased levels of cyclic guanosine monophosphate, cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) were found in samples that were exposed to isosorbide 5-mononitrate compared with control samples. Electron microscopy revealed stromal edema and collagen disorganization after isosorbide 5-mononitrate treatment.. Cyclic guanosine monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2) are involved in nitric oxide-induced cervical ripening. Nitric oxide causes morphologic changes similar to those changes seen during spontaneous cervical ripening.

Topics: Cervical Ripening; Cervix Uteri; Cyclic AMP; Cyclic GMP; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprost; Dinoprostone; Female; Gestational Age; Humans; Immunoblotting; Isoenzymes; Isosorbide Dinitrate; Membrane Proteins; Microscopy, Electron; Nitric Oxide; Nitric Oxide Donors; Pregnancy; Prostaglandin-Endoperoxide Synthases

Nitric oxide (NO) donors are capable of ripening the human cervix during pregnancy. The purpose of this study was to examine how NO donors may be involved in this process. Cervical biopsies were obtained from pregnant women randomized to receive isosorbide mononitrate (n = 10) or no treatment (n = 10) prior to suction termination. Enzyme-linked immunosorbent assays (ELISA) were performed on culture supernatant for interleukin (IL)-1, IL-6, IL-8, IL-10, IL-15, tumour necrosis factor-alpha, monocyte chemoattractant protein-1 and prostaglandin metabolites. Immunohistochemistry was performed to localize these cytokines, cyclooxygenase (COX)-1, COX-2 and prostaglandin dehydrogenase in cervical tissue and reverse transcription-polymerase chain reaction (RT-PCR) to identify COX-1 and COX-2 expression. Biopsies treated with the NO donor isosorbide mononitrate (IMN) produced significantly greater amounts of prostaglandin F(2alpha) in culture and lower amounts of thromboxane B(2) than controls (572.8 versus 34.9 pg/ml, P < 0.05; 53.3 pg/ml versus 530.9 pg/ml, P < 0.01 respectively). The release of other prostaglandins and of cytokines was not affected by treatment with NO. Inflammatory mediators were localized to cervical tissue and COX-1 and COX-2 expression was confirmed by RT-PCR. In conclusion, the mechanism of NO donor-induced cervical ripening during pregnancy may be mediated in part via increased prostaglandin F(2alpha) synthesis.

Topics: Base Sequence; Cervical Ripening; Cervix Uteri; Cyclooxygenase 1; Cyclooxygenase 2; Cytokines; Dinoprost; DNA Primers; Female; Humans; Immunohistochemistry; Isoenzymes; Isosorbide Dinitrate; Membrane Proteins; Nitric Oxide Donors; Pregnancy; Pregnancy Trimester, First; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Reverse Transcriptase Polymerase Chain Reaction; Thromboxane B2