The long term goal is to be able to define on a molecular basis the mechanisms by which the renin angiotensin system is controlled and to be able to identify those hypertensive pathological states in which the renin angiotensin system is a contributor factor. A high molecular weight form of angiotensinogen (H-Aogen) exists in human plasma and amniotic fluid. It is proposed to isolate and characterize H-Aogen from plasma of pregnant women and human amniotic fluid. Monoclonal antibodies directed against H-Aogen will be prepared. An antibody with high affinity to H-Aogen and which does not recognize low molecular weight angiotensinogen (L-Aogen) will be used to develop a radioimmunoassay (RIA) for H-Aogen. The specific antibodies will be used in immunofluorescent staining techniques to determine if cells in the placenta or amniotic fluid contain H-Aogen. If particular cells can be identified as containing H-Aogen, they will be cultured to see if H-Aogen can be produced. The levels of H-Aogen, des-angistensin I(AI)-H-Aogen, L-Aogen and des-AI-L-Aogen in plasma and amniotic fluid of normotensive and hypertensive pregnant women will be determined. An estrogen profile will be obtained on plasma from normotensive and hypertensive pregnant women throughout pregnancy and three values will be correlated with plasma H-Aogen and L-Aogen levels. Urinary catecholestrogen levels will be determined on hypertensive pregnant women. The presence or absence of modifiers or renin in plasma from renovascular hypertensive patients, essential hypertensive patients, uremic patients, and pregnant women will be documented. The development of an animal model for the study of the production and function of H-Aogen will be explored further. The molar ratio of H-Aogen/L-Aogen is significantly altered in 40% of hypertensive pregnant women. These studies will help to define the mechanism responsible for this alteration.
|Lenz, T; Sealey, J E; Tewksbury, D A (1993) Regional distribution of the angiotensinogens in human placentae. Placenta 14:695-9|
|Tewksbury, D A; Tryon, E S (1989) Immunochemical comparison of high molecular weight angiotensinogen from amniotic fluid, plasma of men, and plasma of pregnant women. Am J Hypertens 2:411-3|
|Tewksbury, D A; Tryon, E S; Burrill, R E et al. (1986) High molecular weight angiotensinogen: a pregnancy associated protein. Clin Chim Acta 158:7-12|