ABSTRACT
Effect of genistein, a protein tyrosine kinase inhibitor, on TAME-esterase induced contractions were studied on rat aorta strips in vitro. Data showed that TAME-esterase induced contractions were concentration dependent and these contractions were significantly inhibited when rat aorta strips were pre-incubated with genistein. The present findings provide evidence for the possible contribution of tyrosine kinases during TAME-esterase induced contractions in aorta.
Subject(s)
Animals , Aorta/drug effects , Enzyme Inhibitors/pharmacology , Genistein/pharmacology , Male , Muscle Contraction/drug effects , Peptide Hydrolases/physiology , Protein-Tyrosine Kinases/antagonists & inhibitors , Rats , Rats, Sprague-DawleyABSTRACT
Contractions induced by TAME-esterase on rat aorta strips mounted in vitro were significantly inhibited in presence of Vitamin C. The work lends support to the role of ascorbic acid in preventing endothelial dysfunction through release of nitric oxide. It is suggested that conclusions TAME-esterase could be an important biological marker associated with onset of vascular discases such as hypertension.
Subject(s)
Animals , Aorta, Thoracic/drug effects , Ascorbic Acid/pharmacology , Endothelium, Vascular/drug effects , Muscle Contraction/drug effects , Peptide Hydrolases/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Possible pharmacological effects of N-alpha-tosyl L-arginine methyl ester [TAME] were studied on rat aorta strips in vitro. Results showed that [TAME]-esterase was an endothelium dependent component that involved a nitric oxide cyclic-GMP mediated pathway. Furthermore, during activation of Kinin-Kallikrein system, TAME-esterase induced contractions involve degradation of kinins by kininases.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Aorta, Thoracic/drug effects , Arginine/pharmacology , Captopril/pharmacology , Cyclic GMP/metabolism , Dose-Response Relationship, Drug , Endothelium, Vascular/physiology , Male , Methylene Blue/pharmacology , Muscle Contraction/physiology , Muscle, Smooth, Vascular/physiology , Peptide Hydrolases/pharmacology , Rats , Rats, Sprague-Dawley , Renin , Signal Transduction/physiology , Tosylarginine Methyl Ester/pharmacology , VasoconstrictionABSTRACT
A mathematical model has been proposed to study the effect of [TAME] esterase on blood clotting time. Using this model, clotting time was found to decrease by 30% with increasing plasma [TAME] esterase activity in a group of smokers. It is hypothesized that [TAME] esterase through its effect on Hageman factor could affect clotting time. However mechanism of clotting by [TAME] esterase remains to be elucidated. It is concluded that [TAME] esterase is involved in the cascade of reactions leading to blood coagulation and increased [TAME] esterase activity could be an additional risk factor for possible cerebro-vascular accidents in smokers.
Subject(s)
Adult , Aged , Aged, 80 and over , Biomarkers , Blood Coagulation Tests , Cardiovascular Diseases/epidemiology , Comorbidity , Enzyme Activation , Factor XII/metabolism , Humans , Male , Middle Aged , Peptide Hydrolases/blood , Risk Factors , Smoking/adverse effects , Thrombophilia/enzymologyABSTRACT
Two enzyme inhibitors namely L-NAME, a nitric oxide synthase (NOS) inhibitor and methylene blue, a guanylate cyclase inhibitor, were used to elucidate whether N-alpha-tosyl L-arginine methyl ester (TAME)-induced contractions in toad intestinal rings in vitro are mediated through a nitric oxide (NO)- cyclic GMP (c-GMP) pathway. Moreover, a NO precursor, L-arginine was also used to investigate its effect on TAME-induced contractions. Our findings provide evidence that TAME-induced contractions have both an endothelium-dependent and an endothelium-independent component. Based on our findings we now propose that TAME induced contraction involves an endothelium-dependent component mediated through NO and c-GMP.
Subject(s)
Animals , Bufonidae , Cyclic GMP/physiology , Endothelium, Vascular/physiology , Ileum/blood supply , Methylene Blue/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth/blood supply , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/physiology , Tosylarginine Methyl Ester/pharmacologyABSTRACT
Under in vitro conditions N-alpha-tosyl L-arginine methyl ester (TAME) induced a concentration dependent contractile response on ileal strips with EC50 of 4.3 x 10(-5) M as compared to acetylcholine which induced sustainable contractions with EC50 of 3.2 x 10(-6) M. The present study is the first to demonstrate that TAME is a potent constrictor of non-airway smooth muscle.
Subject(s)
Animals , Bufonidae , Ileum/drug effects , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Tosylarginine Methyl Ester/pharmacologyABSTRACT
Experimental studies show the unique aspects of cytokines profiles in various inflammatory diseases of the lung lead to different clinical manifestations. To elucidate the potential role of cytokines in the pathogenesis of bronchial asthma, plasma interleukins-1 beta, interleukin-6, interferon-gamma and tumour necrosis factor-alpha were measured in 32 asthmatics during an onset of acute asthma. Nine healthy volunteers were included as controls. Cytokine levels were measured by using commercially available ELISA kits. Our results showed that except for interleukin-6, increased concentrations of cytokines were not detected in the controls. Detectable concentrations of IL-6 and TNF-alpha were more common in patients than in controls. However, Interferon-gamma concentrations were below the threshold of detection in both patient and control groups. In conclusions, our results suggest that IL-6 and TNF-alpha are involved during the onset of an acute attack of asthma once the threshold limit has been passed. Hence, these two cytokines are important markers of the inflammatory components of acute asthma.
Subject(s)
Acute Disease , Adult , Asthma/blood , Biomarkers/blood , Cytokines/analysis , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interferon-gamma/blood , Interleukin-1/blood , Interleukin-6/blood , Male , Middle Aged , Skin Tests , Statistics as Topic , Tumor Necrosis Factor-alpha/analysisABSTRACT
Under in vitro conditions atrial natriuretic peptide (ANP) caused specific relation of bronchoconstriction induced by tosyl arginine methyl ester (TAME) on rat trachea. This supports the hypothesis that ANP is a relaxant of airway as well as vascular smooth muscle and since lung tissue contains ANP and ANP receptors, it is hypothesized that the lungs may be a target organ for ANP. It is concluded that ANP had definite bronchodilating properties on rat trachea mounted in vitro and could be a possible antagonist of TAME.