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The effects of angiotensinsI and II on pump-perfusion pressure were examined in the hindlimb vasculature and in the vasculature supplied by the circumflex coronary artery in dogs. In both vasculatures angiotensins I and II caused dosedependent increases in perfusion pressure reflecting directionally similar changes in resistance to blood flow. Responses to angiotensin I were blocked with SQ 20881, a nonapeptide that specifically inhibits conversion of angiotensin I to angiotensin II. In contrast, P-113, a specific anglotensin II antagonist, abolished increases in perfusion pressure produced by angiotensins I and II. These results suggest that increases caused by local administration of angiotensin I in hindlimb or coronary vasculatures are largely ascribable to its enzymatic conversion to angiotensin II. Such conversion appears to occur to the extent of 31% in the hindlimb vasculature, and 26% in the coronary vasculature.

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Graduation date: 1986

Nanophotonics has been proposed to design low latency and high bandwidth Network-On-Chip (NOC) for future Chip Multi-Processors (CMPs). Recent nanophotonic NOC designs adopt the token-based arbitration coupled with credit-based flow control, which leads to low bandwidth utilization. This thesis proposes two handshake schemes for nanophotonic interconnects in CMPs, Global Handshake (GHS) and Distributed Handshake (DHS), which get rid of the traditional credit-based flow control, reduce the average token waiting time, and finally improve the network throughput. Furthermore, we enhance the basic handshake schemes with setaside buffer and circulation techniques to overcome the Head-Of-Line (HOL) blocking. The evaluations show that the proposed handshake schemes improve network throughput by up to 11x under synthetic workloads. With the extracted trace traffic from real applications, the handshake schemes can reduce the communication delay by up to 55%. The basic handshake schemes add only 0.4% hardware overhead for optical components and negligible power consumption. In addition, the performance of the handshake schemes is independent of on-chip buffer space, which makes them feasible in a large scale nanophotonic interconnect design.

Research Doctorate - Doctor of Philosophy (PhD) / There is no consistency between studies of mammalian autonomic systems controlling the coronary circulation, particularly with respect to vagal cholinoceptor activity. Therefore, integrated autonomic control of regional coronary blood flow and conductance was investigated in chronically prepared awake sheep, and compared with data from this laboratory found in the awake dog. Coronary blood flow was measured simultaneously in the circumflex (Cx), right (R) and anterior descending (AD) beds by pulsed Doppler probes. Heart rate (HR) was controlled over the range of 100 to 180 beats/min by atrioventricular pacing. Baroreflex responses were evoked by elevating upper-body aortic pressure (Pa) using an external aortic occluder at HR of 150 and 180 beats/min. Specific agonists determined that effective populations of α-, β-adrenoceptors and cholinoceptors exist in all three coronary beds. Cholinoceptors (ch) and β-adrenoceptors (β) evoke vasodilatation, whereas α-adrenoceptors (α) evoke vasoconstriction. By contrast, electrical vagal stimulation constricts all 3 coronary beds, an effect blocked by methscopolamine. Pacing the heart upward raised baroreflex and metabolic activity and a differential rise in coronary conductance where Cx was greatest followed by R then AD. Block of ch, β and α alone, and together, at different HR revealed that, 1. in all 3 beds an underlying ch constrictor effect is balanced by the summed dilator effects of β, plus a probable α-enhanced vagal, vasointestinal peptide (VIP) interaction mechanism, 2. the net effects summate to enhance flow and conductance in Cx, but not in R and AD. At high HR, there is some waning of the neural mechanisms but raising and sustaining Pa at constant HR can recruit these mechanisms in each bed indicating ch, β and α/VIP, are baroreflex dependent even at the highest physiological HR. Therefore, differences do exist between species, for in particular baroreflex evoked cholinoceptor effects in the mammalian coronary circulation. They are vasoconstrictor in sheep, and vasodilator in the dog. These species differences specify successful alternatives in the evolution of reflex systems to meet the demand for coronary blood flow.

Background: Lipid abnormalities are a common feature of the nephrotic syndrome that is also characterised by oedema, hypoalbuminaemia, proteinuria, and hypercoagulability. Concern has arisen over the increased incidence of cardiovascular disease that has been reported in individuals with nephrotic syndrome, particularly since the syndrome may occur early in life and become a chronic illness. The presence of proteinuria is a prognostic indicator for the progression of renal disease, but its possible contribution as a cardiovascular risk factor in patients with nephrotic syndrome is not known. In contrast, disordered lipoprotein metabolism, in isolation, is a conventional risk factor for the development of atherosclerosis. An early phase of atherosclerosis, vascular endothelial dysfunction, has been identified. Endothelial function can be measured non-invasively using ultrasonography and plethysmography allowing the impact of risk factors to be assessed in vivo.Aim: To test the hypothesis that endothelial dysfunction occurs in the nephrotic syndrome primarily as a consequence of dyslipidaemia.Methods: A cross-sectional design was used to study vascular function of the peripheral circulation in 45 individuals: fifteen patients with nephrosis (NP), 15 control subjects with primary hyperlipidaemia (HL) and 15 normolipidaernic controls (NC). The groups were matched for age, gender and body mass index. The NP group and the HL group had similar serum lipid and lipoprotein concentrations. High-resolution ultrasonography assessed endothelial function of the brachial artery. This non-invasive technique measured post- ischaemic flow-mediated dilatation (FMD) and endothelium-independent vasodilatation in response to glyceryl trinitrate (GTNMD). Post-ischaemic microcirculatory function was measured using venous occlusion strain gauge plethysmography.Results: Post-ischaemic FMD of ++ / the brachial artery was significantly lower in the NP and HL groups, compared with the NC group, with no significant difference found between the former two groups. There were no significant differences in GTNMD of the brachial artery, or in microcirculatory responses. In the patients with nephrosis, non-esterified free fatty acids were inversely associated with FMD, and maximal blood flow with insulin resistance.Conclusion: Dyslipidaemia is associated with endothelial dysfunction in patients with nephrosis and provides a plausible basis for the increased risk of cardiovascular disease observed in individuals with nephrotic syndrome.