Date of Defense

Spring 4-21-2000

Department

Biological Sciences

First Advisor

William F. Jackson, Biological Sciences

Second Advisor

John Spitsbergen, Biological Sciences

Third Advisor

Susan Stapleton, Chemistry

Abstract

20-Hydroxyicosatetraenoic acid (20-HETE), a cytochrome P-4504a metabolite of arachidonic acid and a potent vasoconstrictor has been implicated in the O2-induced constriction of cremasteric arterioles and may act by activation of protein kinase C. As a test of these hypotheses, the author examined the effects of 20-HETE on isolated cannulated cremasteric arteriolar segments and the role of the protein kinase C (PKC) in the signal transduction pathway by which 20-HETE induces vasoconstriction in these arteriolar segments. Application of 20-HETE to the arteriolar segments caused a biphasic vasoconstriction with an initial peak response (-22 ± 7% at 1 µM) followed by partial reversal to a steady-state diameter that remained less than the baseline diameter (-8 ± 7% at 1 µM). The steady-state constriction with 20-HETE in vitro was found to be similar to O2 induced constriction in vivo. In vivo data are from previous studies by the sponsor in which cremaster muscles were studied by intravital video microscopy. However, in the presence of bisindolylmaleimide (BIM) a PKC inhibitor, 20-HETE-induced vasoconstriction was partially inhibited (-67 ± 9% at 0.3 µM). These data support both the hypothesis that 20-HETE may mediate the sustained O2-induced constriction of cremasteric arterioles and the hypothesis that 20-HETE may act through a signal transduction pathway involving protein kinase C.

Access Setting

Honors Thesis-Campus Only

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