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The mesenteric vascular bed from the streptozotocin (STZ) diabetic model was used in this thesis to elucidate the mechanisms underlying diabetic vascular dysfunction. Treatment strategies targeting oxygen free radicals, angiotensin II, and lipids were investigated. In phenylephrine-preconstricted preparations, maximum vasodilation to acetylcholine, progressively deteriorated over 8 weeks of diabetes both before and after NO synthase inhibition which isolated the EDHF component. Chronic preventive treatment with silymarin, a free radical scavenger, or allopurinol, a xanthine oxidase inhibitor, partially protected against the development of 4-week diabetic deficits of the NO and EDHF systems. On the other hand, treatment with the semicarbizide-sensitive amine oxidase (SSAO) inhibitor, MDL74972A, only significantly improved the NO component. Preventive treatment with the transition metal chelator, trientine, produced significant protection of the NO and EDHF responses. Furthermore, intervention treatment not only protected against the development of an 8-week but also reversed some of the 4-week diabetic deficit. Both preventative and intervention treatments targeting angiotensin II production through either angiotensin-converting enzyme (ACE) inhibition with lisinopril or AT1 receptor blockade with candesartan provided some protection against the diabetic-induced decline in acetylcholine relaxations. Most notably, candesartan preventive treatment completely protected against a deficit in the EDHF response. Preventive treatment with rosuvastatin, a lipid-lowering drug, partially protected against the development of NO and EDHF deficits. The results show that experimental diabetes had deleterious effects on NO and EDHF-mediated vasodilation and suggest a role for free radicals, angiotensin II and lipids in this dysfunction.

Solid solutions of general formula La1.5-xBa1.5+x-yAyCu3Oz (A=Ca, Sr) have been studied. These form over the complete composition range 0x0.5, 0y0.5, excluding compositions centred on the La-123 composition, LaBa2Cu3Oz. The solid solutions have properties which range from semiconducting (x=y=0) to superconducting, with Tc (max.) = 78K for the composition LaBa1.5Ca0.5Cu3O7.01, and were found to be tetragonal across their entire range. Rietveld refinement of X-ray powder data has shown that whereas Sr occupies the Ba site, Ca occupies the La site with concomitant displacement of La onto the Ba site. The magnetic behaviour and oxygen contents of these solid solutions are discussed. The variation of Tc with oxygen content has been studied for the composition LaBa1.5Ca0.5Cu3Oz; for quenched samples, Tc varies linearly with oxygen content, but slow cooled samples show a "Double Plateau" behaviour, and thus Tc depends critically upon the cooling regime. Analogues RE1.5-xBa1.5+x-yCayCu3Oz (RE = Nd, Pr, Sm, Eu, Gd and Dy) have also been studied; the extent of the solid solution decreases with decreasing size of rare earth. For Dy, no appreciable solid solubility was observed. For Nd and Pr, the solid solutions centre on the 336 composition La1.5Ba1.5Cu3Oz; for the smaller rare earths this composition cannot be prepared in air, and the solid solutions are centred on the orthorhombic, REBa2Cu3Oz phase. All were found to be superconducting except the Pr-based solid solutions; results suggest that these contain Pr4+ as well as Pr3+. In the solid solutions RE1+xBa2-xCu3Oz (x0, RE = Sm, Eu and Gd), critical temperatures exhibit a marked dependence on the size of the A-site cations.