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Increased Vascular Generation of Thromboxane A 2 : an Initiating Condition for Microvascular Rarefaction in Obese Zucker Rats?
Author(s) -
Goodwill Adam G.,
Stapleton Phoebe A.,
Frisbee Stephanie J.,
James Milinda E.,
Frisbee Jefferson C.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.774.19
Subject(s) - rarefaction (ecology) , microvessel , medicine , endocrinology , vasodilation , chemistry , bioavailability , pharmacology , angiogenesis , biology , ecology , species diversity
Our studies have demonstrated that rarefaction of the skeletal muscle microcirculation in OZR with evolution of the metabolic syndrome is well predicted by a chronic reduction to vascular nitric oxide (NO) bioavailability. However, prior to any loss in NO, skeletal muscle vessels from OZR exhibit a shift in arachidonic acid metabolism, with an increased production of TxA 2 over PGI 2 . Temporal analyses indicate that this early increase in vascular TxA 2 production/action is associated with an initial early rarefaction of 5–7%. If NO bioavailability is maintained (TEMPOL) after the initial increase in TxA 2 and microvessel loss, the total rarefaction magnitude is blunted. Alternately, if actions of TxA 2 are chronically inhibited, the initial rarefaction never develops and the subsequent secondary pulse (from NO reductions) is strongly muted. Chronic treatment with pentoxyfillene (to prevent TNF‐α production) or HMG CoA reductase inhibitors (atorvastatin/simvastatin) prevented much of the secondary pulse of rarefaction (associated with maintenance of NO bioavailability), yet did not alter either the shift in TxA 2 production or the initial rarefaction. These results suggest that microvessel rarefaction in OZR represents the integration of an early mild vessel loss that is dependent on TxA 2 , which creates an environment for the extensive rarefaction that is dependent on low NO bioavailability. (NIH DK64668)