Salt sensitivity of blood pressure is a substantial risk factor for cardiovascular morbidity
and mortality. Inappropriate increases in renal sodium reabsorption lead to volume expansion,
hypertension and salt sensitive blood pressure. Key homeostatic mechanisms that regulate
renal sodium reabsorption are: first, hormonal, e.g., renin-angiotensin-aldosterone system
and second, vascular, e.g., renal vasculature. Dysfunction in one or both mechanisms leads to
hypertension and salt sensitive blood pressure. The investigators recently documented that
striatin plays a novel role in the development of salt sensitive blood pressure. However, the
mechanisms that lead to striatin-mediated salt sensitive blood pressure are not clear;
defining these mechanisms is the overall goal of this proposal.
Striatin is a calmodulin- and caveolin-binding protein that can function as either a
scaffolding and/or signaling protein, specifically in relation to the mechanism of action of
steroids. In a large study of well characterized subjects from the HyperPATH cohort, the
investigators documented that hypertensive and normotensive humans who are striatin risk
allele carriers have salt sensitive blood pressure.
The investigators then developed a striatin heterozygous knockout mouse as a tool to identify
potential mechanisms for the salt sensitive blood pressure. The investigators documented that
these mice also have salt sensitive blood pressure with higher blood pressure levels and
inappropriately increased aldosterone levels on a liberal salt diet.