Semester

Fall

Date of Graduation

2007

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Cardiovascular and Thoracic Surgery

Committee Chair

Matthew A Boegehold

Committee Co-Chair

Jefferson C Frisbee

Abstract

Growth of the arteriolar network is accompanied by progressive changes in pressure and flow, and in the metabolic environment to which the arterioles are exposed. This dissertation was carried out to investigate the extent to which mechanisms involved in local blood flow regulation may also change during this growth. We isolated gracilis muscle arterioles from weanling (age 25-26 days) and juvenile (44-66 days) rats, and studied the responsiveness of these vessels to both myogenic and endothelium-dependent stimuli. Overall arteriolar responses to the endothelium-dependent agonists acetylcholine (ACh), A23187, VEGF and simvastatin were not different between age groups. Responses of juvenile arterioles to ACh and simvastatin were significantly reduced by inhibition of nitric oxide synthase or cyclooxygenase, by the hydrogen peroxide scavenger catalase, and by potassium channel inhibition. Responses of weanling arterioles to ACh and simvastatin were unaffected by these treatments, but significantly reduced by heme oxygenase inhibition. Arteriolar growth during juvenile maturation is accompanied by an increase in myogenic responsiveness, possibly because endothelium-derived PGH2 or TXA2 assumes a role in reinforcing myogenic activity over this period. In conclusion, mediators of endothelium-dependent dilation change during growth, with carbon monoxide contributing largely to these responses in young animals, and a combination of nitric oxide, prostanoids and hydrogen peroxide contributing to these responses in older animals. These data suggest that age-dependent differences in the control of vascular tone exist and may have significant implications for the regulation of tissue perfusion.

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