The role of angiotensinogen in the pathophysiology of hypertension

Essential hypertension is an important cause of human cardiovascular morbidity and mortality in most developed countries. Analysis of hypertensive siblings has revealed significant genetic linkage and alleilic association between angiotensinogen, the precursor of angiotensin II, and essential hypertension. Angiotensinogen is one of the components of the renin-angiotensin system that plays a central role in blood pressure regulation. Beside the circulating system, multiple tissue renin-angiotensin system including in arterial wall, heart, brain, and kidney have been described. Transgenic models confirmed a direct, causal relationship between increased angiotensinogen gene copy number and increased arterial pressure. Nevertheless, the site of action of angiotensinogen overexpression on increased pressure remains only speculative. We proposed to identify the role that individual renin-angiotensin systems have on the hypertensive phenotype by creating animal models with altered tissue-specific angiotensinogen expression. Furthermore, for a better understanding of the renal system, we will investigate the regulation and its interaction with other systems involved in blood pressure homeostatsis.