Mechanisms contributing to the inter-individual variability in neuro-cardiovascular responses to exercise

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Blood pressure (BP) is essential to maintain organ perfusion and a key regulated variable of the cardiovascular system. Despite this importance, large variability in BP exists between healthy individuals at rest and in response to exercise. Finding the mechanisms responsible for these inter-individual differences is a long-term goal of my research program. Preliminary data from my laboratory has found several novel mechanisms for variability in exercise muscle sympathetic nerve activity (MSNA) and BP responses. We have shown important roles of genetic differences in chemical receptors in muscle for regulating exercise BP in young men but not women. We will now study the mechanism responsible for this sex difference and examine the influence of stretch sensitive muscle receptors. We have also shown that maximal muscle strength (absolute force) influences BP responses to relative intensity static handgrip exercise, challenging current dogma. Our proposed work will determine if these findings apply to larger muscle mass leg exercise or dynamic modes of contraction. The sympathetic nervous system is key for the regulation of BP, but we found that MSNA responses are unrelated to BP responses during exercise. Instead, we showed that the MSNA responses to exercise were related to the relative changes in BP loading. This suggests an important role of the arterial baroreflex in these responses. Our results found key differences in this regulation during two different types of exercise, static vs. dynamic handgrip contractions. We must now investigate what is the cause of these differences. A lingering question that remains is why increases in MSNA are poorly related to BP responses during exercise. Sympathetic outflow can be differentially controlled to distinct organ beds (e.g. heart, muscle, kidneys) and total sympathetic outflow may be similar between individuals but relative outflow to muscle could be different. We will study whether changes in sympathetic outflow to muscle and the kidneys are inversely related during exercise. Our preliminary findings have raised stimulating new questions that highlight our incomplete understanding of the mechanisms controlling sympathetic and BP responses to exercise. The short-term objectives of this proposal are to examine the influence of genetic variations, absolute muscle force, arterial baroreflex control of MSNA, and differential control of sympathetic outflow on BP responses during exercise. We will employ an integrative approach and conduct all proposed research in human participants. The new knowledge generated will significantly advance our fundamental understanding of the mechanisms controlling sympathetic and BP responses to exercise in humans. This will have applications for all cardiovascular fields. The proposed research program will also provide a high-quality and multi-faceted HQP training environment focused human integrative neuro-cardiovascular physiology.