Grant: Discovery Grants Program - Individual

The sympathetic nervous system is an important regulator of moment-by-moment changes in blood pressure through changes in vascular contractile state. This system emits bursts of sympathetic nerve activity (SNA) consisting of multiple neurons discharging at more-or-less the same time. This research program tests the working hypothesis that the discharge patterns of SNA variously impact vasomotor control through the differential release of multiple neurotransmitters. The major objectives are: 1) Quantify the coded patterns of neuronal action potentials present within integrated bursts of SNA, their reflex-specificity, and their species-specificity. Wavelet denoising methods and other Matlab-based algorithms will be used to expose and characterize individual action potentials in the multi-unit nerve recordings. 2) Establish the receptor-based mechanisms that differentially affect the mechanical properties of the vascular tree in skeletal muscle. Using a modified Windkessel model, the lumped parameters of resistance, compliance, viscoelasticity and inertia will be measured in the skeletal muscle of the human forearm and the rat hindlimb during reflexive manoeuvres along with their receptor-based mechanism of control. 3) Quantify the impact of physiologically relevant SNA discharge patterns on vasomotor mechanics and their post-junctional receptor-based mechanism of control, emphasizing baroreflex versus muscle chemoreflex activation. We will simulate patterns of SNA action potentials that replicate SNA bursts of varying sizes, groupings, and inter-burst spacing. These will be played back into the femoral nerve of an anesthetized rodent and the impact on receptor-based changes in vascular resistance and compliance will be measured. The experiments will provide novel and innovative approaches to examine the manner in which sympathetic neurons communicate with blood vessels to exert short-, and longer-term vascular control. These studies embrace integrative animal physiology and offer a unique opportunity for scientific discovery and for training of highly qualified personnel.