ABSTRACT
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
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
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.