Dilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M₂ subtype. Inhibition of [³H](-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. Both aortic ring segments and perfused caudal arteries showed an age-related increase in sensitivity of endothelium-mediated relaxation to the cholinergic agonist methacholine. This increased sensitivity occurs between the ages of 6 and 12 months, with no further significant increase up to 27 months of age, suggesting this is a consequence of growth and development rather than old age. No difference with age in cholinergic relaxation was observed in the perfused mesenteric bed indicating either no change of sensitivity in smaller resistance vessels or an effect which is hidden in this more complex perfused system. In contrast to findings with cholinergic stimution, responses of the perfused caudal artery to the calcium ionophore A23187 were not altered with age. This suggests that the alteration with age in response to methacholine involves the muscarinic receptor or receptor coupling mechanism rather than the generation of, or response to, endothelium-derived relaxing factor (EDRF). The influence of endothelium on contractile responses was examined using the perfused caudal artery. Endothelium removal significantly increased contraction to the α-adrenergic agonists methoxamine and BH-T 920 as well as to transmural nerve stimulation. Inhibition of contraction to agents which must first cross the smooth muscle layer before reaching the endothelium suggests that a continuous or basal level of EDRF release is responsible for decreased contraction rather than an receptor stimulated release of EDRF.

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In this climate of declining budgets and resources, models and simulations (M&S) have become very beneficial to the U.S. Navy. However, the U.S. Navy's investment in, and use of, M&S for addressing critical operational issues (COIs) within a warship's operational test (OT) program would not be practical unless the particular M&S was determined to be a credible representation of that which would be physically tested. Commander Operational Test and Evaluation Force (COMOPTEVFOR) is responsible for accrediting U.S. Navy M&S that are required to support OT. COMOPTEVFOR has developed a VV and A process that is documented in COMOPTEVFORINST 5000.1A. This instruction requires all surface ship acquisition program managers (PMs) to develop a Validation and Verification (V and V) plan that would meet COMOPTEVFOR's expectations for likely accreditation. This thesis will identify the extent to which surface ship PMs are complying with COMOPTEVFORINST 5000.1A; why they are not in full compliance with the instruction; what incentives would help them comply with the instruction; and what improvements can be made to the instruction that would increase compliance by the PMs. Finally, this thesis will conclude with recommendations that would help increase compliance with the instruction by the PMs. / Department of the Navy (civilian) authors.

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Thesis (M.Res.(Med.))--University of Hong Kong, 2009. / Includes bibliographical references (p. 73-99).

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / Typescript. Vita. Includes bibliographical references (leaves 132-143). Also available on the Internet.

Thesis--Københavns universitet. / Includes bibliographical references.