Thesis (M.S.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains viii, 37 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 33-37).

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Thesis (M.D.)--University of Hong Kong, 1995. / Includes bibliographical references (leaf 172-203). Also available in print.

Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

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Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (M.Sc.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Experimental Medicine, Department of Medicine. Title from pdf file main screen (viewed on January 17, 2010). Includes bibliographical references.

Endothelin-1 (ET-1) binds to endothelin A (ETA) and B (ETB) receptors on vascular smooth muscle cells, resulting in profound vasoconstriction and cellular proliferation. In contrast, activation of endothelial cell (EC) ETB receptors releases nitric oxide (NO) and prostacyclin (PGI2), which are anti-mitotic and mediate vasodilatation. ETB receptors are also responsible for the clearance of ET-1 from the circulation and renal ETB receptors contribute to sodium and water balance. Pharmacological blockade and genetic models featuring total ETB ablation, demonstrate salt sensitive hypertension. However, these do not allow the role of the EC ETB in cardiovascular homeostasis to be determined. Mice featuring loxP sites flanking exons 3 and 4 of the ETB gene (floxed ETB mice: FF/--) were crossed with Tie2-Cre mice (WW/Tie2-Cre), in which the expression of a Cre recombinase cDNA transgene is limited to EC, to generate EC-specific ETB down-regulated mice (FF/Tie2-Cre). Having demonstrated EC-specific down-regulation of ETB receptors using autoradiography, the role and relative contribution of the EC ETB to the regulation of systemic BP, to the clearance of ET-1 from the plasma, as well as to the development of pulmonary arterial hypertension were investigated. Autoradiography revealed significant down-regulation of ETB in EC-rich tissues such as lung of FF/Tie2-Cre animals (8 ± 3 amol.mm-2) compared to controls (80 ± 21 amol.mm-2) (n=4; p<0.05). Levels of ETA expression were preserved despite higher concentrations of plasma ET-1 in the FF/Tie2-Cre samples (12.4 ± 3.0 pg.ml-1) compared to controls (3.0 ± 0.8 pg.ml-1) (n=6; p<0.001). Using radiotelemetry, mean arterial blood pressure of FF/Tie2 mice was not significantly different to that of FF/- controls on low salt (FF/Tie2-Cre: 122.7 ± 1.52 mmHg, n=10; FF/--: 125.7 ± 0.58 mmHg, n=12), normal salt (FF/Tie2-Cre: 133.8 ± 4.0 mmHg, n=10; FF/--: 131.5 ± 3.33 mmHg, n=12) or high salt diet (FF/Tie2-Cre: 149.2 ± 2.71 mmHg, n=10; FF/--: 143.9 ± 2.97 mmHg, n=12). Similarly no differences in SBP, DBP or HR were seen between genotypes. The clearance of an intravenous bolus of radiolabelled ET-1 was significantly impaired in FF/Tie2-Cre mice (0.054 ± 0.006 ml.sec-1) compared to control mice (0.175 ± 0.032 ml.sec-1) (n=5; p<0.01). ETB blockade of control mice reduced ET-1 clearance to that of untreated FF/Tie2-Cre animals (n=4). Two weeks of hypobaric hypoxia induced an exaggerated increase in systolic right ventricular pressure in FF/Tie2-Cre mice (34.4 ± 1.2 mmHg, n=10) compared with FF/-- mice (24.6 ± 1.4mmHg, n=10; p<0.05), associated with an increased right ventricular/ left ventricular + septum ratio in FF/Tie2-Cre mice (normoxia: 0.224 ± 0.009; hypoxia: 0.285 ± 0.017; p<0.01), but not in FF/-- mice. Hypoxia increased the percentage of remodeled vessels in FF/-- mice (normoxia: 5.6 ± 0.6%; hypoxia: 11.4 ± 0.6%; n=6; p<0.001), and this was augmented in FF/Tie2-Cre mice (normoxia: 7.1 ± 0.5%; hypoxia: 18.5 ± 1.2%; n=6; p<0.001). The EC ETB receptor does not play a significant role in the BP response to salt, suggesting that ETB signalling on other cell types is responsible for ETB mediated natriuresis. However, the EC ETB receptor is crucial to the elimination of ET-1 from the circulation and is protective against the development of pulmonary arterial hypertension, most likely by preventing remodeling of small pulmonary arteries.