“MR Antagonist and STRIATIN”
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.
Drug - Eplerenone vs Amlodipine
We posit that decreases in striatin activity/levels increases aldosterone secretion resulting in hypertension and salt sensitive blood pressure. Thus, our mechanistic clinical study will assess whether hypertensive striatin risk allele carriers will show significantly greater reductions in blood pressure with a specific aldosterone mediated treatment approach (mineralocorticoid receptor blockade) than with a non-specific approach (amlodipine). To test this hypothesis, we will perform a randomize ...read more on ClinicalTrials.org
Salt Sensitive Hypertension and Striatin