Semester

Summer

Date of Graduation

2008

Document Type

Dissertation

Degree Type

PhD

College

College of Physical Activity and Sport Sciences

Department

Exercise Physiology

Committee Chair

Judy M Muller-Delp

Abstract

The purpose of the first study was to determine how age and ovarian hormones affect flow-induced vasodilation in the coronary microcirculation. Coronary arterioles were isolated from young, middle-aged, and old control, ovariectomized (OVX) and ovariectomized + estrogen replaced (OVE) female Fischer-344 rats to assess vasodilation to increases in flow. L-NAME, a nitric oxide synthase (NOS) inhibitor, was used to assess NO contribution to flow-induced dilation (FID). FID of coronary arterioles was impaired with advancing age. Ovariectomy reduced FID in young females only; however, estrogen-replacement restored or improved FID in all age groups. FID was reduced after pretreatment with L-NAME in young control and all estrogen-replaced groups, indicating these dilator responses were mediated through nitric oxide (NO). Increasing age caused an impairment of FID which corresponds to an age-related loss in NO-mediated dilation in the coronary microcirculation of female rats. FID in aged females appears to be impervious to OVX; however, estrogen-replacement improves FID by ∼ 160% versus old control and OVX.;The second study evaluated vasoconstriction to endothelin in coronary arterioles from young and old male and female Fischer-344 rats. BQ123, an ETa receptor inhibitor, or BQ788, an ETb receptor inhibitor, was used to assess receptor-specific contributions to ET-induced vasoconstriction in intact and endothelium-denuded arterioles. Males exhibited an age-related decline in vasoconstriction to ET in coronary arterioles which is associated with a decline in ETa receptor mRNA and protein expression. Arterioles from females demonstrated increased ET-induced vasoconstriction with advancing age, but this is not associated with an age-related alteration in ETa or ETb receptor mRNA or protein expression. Aging differentially alters vasoconstriction to ET in coronary arterioles from males and females, and this may contribute to the gender-related differences in the development of cardiovascular risk with aging.

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