HyperK · Differential effects of dietary potassium intake on blood pressure

As the primary risk factor for the onset of cardiovascular disease, hypertension is a major contributor to premature death and disability. High dietary sodium (Na+) consumption is often considered a primary culprit for hypertension, but evidence exists that increasing dietary potassium (K+) consumption may lower blood pressure (BP). However, a number of studies in humans indicate that higher K+ intake is not always beneficial for blood pressure effects that the host lab recently confirmed in rodents. Reducing and maintaining a lower BP based on dietary intervention requires understanding of the long term and/or accumulated effects of the intervention and the underlying molecular basis. This project will increase our understanding of the differential effects of dietary K+ on BP, the role of the kidney and potentially the vasculature. The project objectives are to: 1) determine the optimum dietary K+ intake that reduces and sustains lower BP; 2) identify factors in the kidney that drive K+ sensitivity of BP; 3) assess if sustained high dietary K+ intake changes vascular function; 4) investigate the molecular basis of any vascular remodelling that promotes, or is consequential, to increased BP during prolonged high dietary K+ intake. To address these questions I will apply a broad range of interdisciplinary skills and methods: telemetric monitoring of BP, in vivo assessment of kidney and vascular function in animal models and gene modified mice, RNA sequencing (including single-cell) and bioinformatics, optical clearing and innovative 3D multiplex imaging of tissues. Successful completion of the research in this proposal provides an excellent opportunity to uncover new targets and strategies for the management of hypertension. From a personal perspective it represents a major step towards establishing myself as an independent researcher in the area of renal-vascular crosstalk.