CONTRACTILE BEHAVIOR OF NEW BORN LAMB LEFT ANTERIOR DESCENDING CORONARY ARTERY (LAD) IS REGULATED BY PROTEIN TYROSINE KINASE-DEPENDENT MECHANISM† 130

The complex post-receptor signaling events which ultimately regulate coronary circulation during perinatal development remain to be elucidated. Protein tyrosine kinase (PTK;ATP:protein-tyrosine-O-phosphotransferase) plays a key role in intracellular signal transduction associated with vascular growth, development and function. In order to test the hypothesis that contractile behavior of newborn lamb LAD may be regulated by PTK- and/or protein tyrosine phosphatase (PTP)-dependent mechanisms, we evaluated, using tissue chamber technique, the effect of genistein[G], an inhibitor of PTK, and sodium orthovanadate [SOV], an inhibitor of PTP, on isolated LAD preparations(wet weight≈0.9 mg). [SOV](50, 100, 500 μM) stimulated contraction of LAD in a dose-dependent manner (0.05±0.03, 0.21±0.08, 1.09±0.23 g/mg tissue, respectively; which was equal to 13%, 47%, 111% of the maximal response to 120 mM KCl, respectively). [G] pretreatment (100μM) completely suppressed the SOV-induced contraction (0.01±0.02,-0.07±0.04,-0.02±0.05 g/mg tissue, respectively). In additional experiments, [G] reduced (from 0.33±0.12g/mg to 0.05±0.02 g/mg,≈85%) the contractile response of LAD to angiotensin II [A] (100 nM). However, [SOV] (500 μM) augmented (from 0.35±0.07g/mg to 0.42±0.07 g/mg, ≈21%) the [A]-induced contraction. Based on these data, we conclude that PTK/PTP-dependent signal transduction pathway(s) may be an important factor in the regulation of the basal tone and in the post receptor signaling associated with [A]-induced force generation in LAD of newborn lamb. {Supported by American Heart Association national council,#95009270}

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Castro, E., Kim, S., Oue, X. et al. CONTRACTILE BEHAVIOR OF NEW BORN LAMB LEFT ANTERIOR DESCENDING CORONARY ARTERY (LAD) IS REGULATED BY PROTEIN TYROSINE KINASE-DEPENDENT MECHANISM† 130. Pediatr Res 39, 24 (1996). https://doi.org/10.1203/00006450-199604001-00149

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