Effects of sympathetic nerve activity on the stiffness of conduit arteries

Sympathetic nerve activity (SNA) regulates blood pressure by controlling vascular smooth muscle tone in peripheral arterioles. However, the function of SNA on vascular smooth muscle affecting the function of large conduit arteries is not as well established. It is hypothesized that SNA modulates smooth muscle tone, differentially loading the passive structural elements of the aortic wall, leading to changing arterial stiffness. This thesis presents a series of in-vivo experimental studies which aim to quantify the contribution of SNA on arterial stiffness. Techniques developed for quantification of arterial stiffness involved high fidelity measurements of diameter and pressure in the rat aorta. Sympathetic denervation was performed in different rodent strains (normotensive, WKY; hypertensive, SHR; hypertensive kidney disease and increased calcification, LPK) with varied baseline SNA to ascertain the effects of both chronic and acute changes in SNA. Denervation was achieved by unilateral splanchnicectomy or ganglionic blockade with hexamethonium. Aortic stiffness measurements (pulse wave velocity, compliance, distensibility) were performed across a range of mean arterial pressures to characterise the pressure dependent effect of SNA on stiffness of the abdominal aorta. Phase relationships between pressure and diameter enabled characterisation of neurogenic effects on wall viscoelasticity. Findings showed that: (i) unilateral physical denervation is insufficient to produce a change in stiffness of the abdominal aorta; (ii) sympathetic denervation by ganglionic blockade produces a maximal decrease in aortic stiffness at resting blood pressure in WKY rats; (iii) chronic exposure to high blood pressure induces vascular remodelling which alters aortic diameter, reducing the effect of SNA in SHR; (iv) modulation of cardiac function due to SNA can significantly affect arterial viscoelasticity by altering the dynamic loading characteristics of the wall of conduit arteries; this effect is more pronounced in LPK rats; (v) pressure-distension profile in the rat aorta is distinctly different to that in human arteries due to the large difference in heart rate. These findings demonstrate that the effect of SNA on arterial stiffness is mediated by direct neurogenic effect on arterial smooth muscle tone and by effects on cardiac contraction affecting the dynamic loading of conduit arteries.