CONTRACTILE RESPONSE OF NEWBORN LAMB PULMONARY ARTERY (PA) TO SEROTONIN AND HISTAMINE IS ASSOCIATED WITH PROTEIN TYROSINE KINASE- AND NITRIC OXIDE-DEPENDENT MECHANISMS † 2062

The purpose of the present study is to determine if contractile property of PA is regulated by protein tyrosine kinase [PTK])- and nitric oxide[NO]-dependent signaling systems. We preliminarily evaluated, using tissue chamber technique, effects of genistein[G], a PTK inhibitor, and SNAP[(+/-)-S-Nitroso-N-acetylpenicillamine], an NO donor, in histamine[H]](100 μM)- and serotonin [S](1 μM, 10 μM)-challenged PA preparations (wet weight ≈0.75mg, initial load 1g) as a model. [G](20μM, 80 μM) dose-dependently relaxed [S](10 μM)-induced maximum contraction (0.73±0.03 g/mg tissue) to (0.57±0.01, 0.01±0.01 g/mg, respectively; equal to 22%, 98% relaxation) and[H]-induced maximum contraction (0.16±0.09 g/mg) to (-0.05±0.04,-0.09±0.07 g/mg, respectively; equal to 160%, 286% relaxation). SNAP(1μM, 10 μM) relaxed [S](10 μM)-induced maximum contraction(0.92±0.03 g/mg) to (0.38±0.14, 0.17±0.02 g/mg, respectively; equal to 58%, 78% relaxation) in dose-dependent manner. Interestingly, [G](20 μM)-induced relaxation of both [S]- and [H]-induced contraction had a slow onset but was steady and sustaining while SNAP caused rapid relaxation of both [S]- and [H]-induced contraction. SNAP-induced relaxation of [S]-contraction was partially and dose-dependently recovered. LY-83583, an inhibitor of NO-induced activation of soluble guanylate cyclase, reversed SNAP-induced relaxation of both [S]- and [H]-contraction. In contrast, SOV reversed [G]-induced relaxation of both [S]- and[H]-contraction. L-NAME (100 μM), NO synthase (NOS) inhibitor, did not effect SNAP- or Zaprinast [Z](c-GMP phosphodiesterase inhibitor)-induced relaxation. [Z](10 μM) further enhanced SNAP-induced relaxation of[S](1μM)-contraction. Diphenyleneiodonium chloride (DPI) (5 μM), another NOS inhibitor, showed a similar effect of [Z]. Based on these data, we conclude that contractile property of isolated newborn lamb PA is regulated by PTK mediated signal transduction pathway(s) and that [S]- and [H]-induced contraction in this paradigm is associated with PTK-dependent mechanisms and linked to NO-responsive element(s). {supported in part by Institute for Korean-American Studies; American Heart Association, national council#95009270}

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Que, X., Kim, S., Russo, P. et al. CONTRACTILE RESPONSE OF NEWBORN LAMB PULMONARY ARTERY (PA) TO SEROTONIN AND HISTAMINE IS ASSOCIATED WITH PROTEIN TYROSINE KINASE- AND NITRIC OXIDE-DEPENDENT MECHANISMS † 2062. Pediatr Res 39, 346 (1996). https://doi.org/10.1203/00006450-199604001-02086

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