Abstract

Hypertension (high blood pressure) affects 1 in 4 over the age of 25 years, contributing to an estimated 12.8% of global deaths. Despite its prevalence and the abundance of research, in approximately 95% of cases the exact cause remains unknown.

My work aims to elucidate the regulatory mechanisms of salt handling by the kidney’s distal tubules and the subsequent blood pressure changes due to water loss/retention. Of particular interest is the Na+Cl Cotransporter (NCC), the primary target of anti-hypertensive thiazide diuretics, often considered to be the first-line defence. Although NCC was once thought static and unchanging, recent studies have revealed a complex and dynamic network of regulatory proteins such as WNK , SPAK, and OSR1 controlling NCC activity. My talk will discuss the newly discovered MO25 α master regulator and its interactions with the WNK -SPAK/OSR1-NCC signalling cascade, some new insights into thiazide mechanisms of action, as well as the potential for new and exciting therapeutic targets.