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Mechanisms Underlying Combined Effects of Hypertension (HTN) and Hypercholesterolemia (HCh) on Microvascular Function
Author(s) -
YILDIRIM Alper,
Dozier Alton L.,
Granger D. Neil
Publication year - 2013
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.27.1_supplement.902.1
Subject(s) - proinflammatory cytokine , cremaster muscle , oxidative stress , reactive oxygen species , medicine , endocrinology , angiotensin ii , intravital microscopy , microcirculation , inflammation , chemistry , blood pressure , biochemistry
HTN and HCh are known to initiate inflammatory and thrombogenic responses in the microvasculature. However, little is known about whether, and how, combinations of risk factors (e.g., HTN+HCh) alter microvascular function. In this study we examined how the combined actions of HTN and HCh on the microvasculature differ from the responses to either risk factor alone. Intravital video microscopy was used to monitor the adhesion and emigration of leukocytes and the oxidation of dihydrorhodamine (a measure of oxidative stress) in cremaster muscle post‐capillary venules of wild type (WT) mice that were either infused with angiotensin II (AngII) for 2 wks (HTN), placed on a high cholesterol diet (HCh), or both (HTN+HCh). Either HTN or HCh alone promoted the recruitment of leukocytes and enhanced the production of reactive oxygen species (ROS) in venules. However, the combination of HTN and HCh produced changes in leukocyte recruitment and ROS production that were greatly attenuated compared to HTN alone. The changes in leukocyte adhesion and ROS production were not observed in HTN+HCh mice rendered neutropenic with anti‐neutrophil serum. The inhibitory effect of HCh on the AngII mediated responses was not mimicked by administration of an apoA‐I mimetic (4F). These findings indicate that HCh counteracts the proinflammatory effects of AngII via a mechanism that involves diminished ROS production. (Supported by HL26441).