Effects of Vascular Nitric Oxide Bioactivity and Vascular Ageing on Arterial Blood Pressure and Flow Waveforms

Abstract

Analysis of blood pressure and flow waveforms may lead to improved diagnosis of arterial dysfunction and disease. This thesis describes experiments to investigate the characteristic alteration of peripheral waveforms produced by stimulated release of vascular nitric oxide (an effect that is attenuated by endothelial dysfunction) and the changes that occur with age. In vivo experiments were conducted in anaesthetised rabbits and in vitro experiments employed a polyurethane model of the human aorta and its principal branches. Blood pressure, blood flow, pulse wave velocities and vessel diameter were recorded in the rabbit abdominal aorta. Equivalent recordings were obtained from the model aorta. Data were analysed in the time domain using wave intensity analysis after separation of reservoir (Windkessel) pressure and wave pressure. Effects of acetylcholine (Ach) and NG-nitro-L-arginine methyl ester (L-NAME) were investigated in vivo. Ach (which promotes endothelial production of nitric oxide) increased wave reflection, whilst L-NAME (which inhibits nitric oxide production) decreased it. These trends were opposite to the expected ones, and do not account for the established effects of nitric oxide on peripheral arterial waveforms. Further work is required to investigate these contradictions. Arterial stiffening in immature and mature rabbits was attempted by supplementing their diet with fructose. Fructose is known to form advanced glycation end-products in arterial walls and hence to stiffen arteries. Unexpectedly, fructose did not affect haemodynamic function. However, immature control rabbits had markedly reduced aortic wave reflection compared to mature control rabbits, indicating that the former have arterial impedances that are better matched for incident wave propagation. Wrapping the model aorta in Clingfilm was used to simulate age- or drug-induced stiffening of the aorta in vivo. Increased pulse pressure was observed, resembling the isolated systolic hypertension prevalent in aged populations. The model has potential for modelling haemodynamic function in health and disease.