Endocrinology, Diabetes and Hypertension

Gail Adler, M.D., Ph.D.

Dr. Adler is studying the role of the mineralocorticoid receptor (MR) in cardiovascular pathology. Recent data from her laboratory and others document that MR activation is associated with cardiac hypertrophy, fibrosis, nephropathy and strokes in experimental animals.  Her research is directed at elucidating the molecular and cellular mechanisms underlying these effects using several animal models: 1) nitric oxide synthase inhibition with ANGlI and dietary Na⁺ supplementation; 2) uni-nephrectomy with aldosterone and dietary Na⁺ supplementation; 3) streptozotocin treatment (a model of type 1 diabetes mellitus); 4) the db/db mouse (a model of type 2 diabetes mellitus); 5) several genetically manipulated mouse models.  Experiments are being conducted to define the role of modulators and/or intermediaries of MR-induced cardiovascular damage, including estradiol, ANGlI, PAl-l, and the receptor for advanced glycosylation end products. Finally, these laboratory based studies provide a scientific foundation for studies being conducted in patients  to determine the effects of MR antagonists on renovascular and cardiovascular function in diabetes.

Selected References:

1. Rocha R, Stier CT Jr., Kifor I, Ochoa-Maya M, Rennke HG, Williams GH, Adler GK.  Aldosterone:  A mediator of myocardial necrosis and renal arteriopathy.  Endocrinology 2000; 141:3871-3878.
2. Martinez DV, Rocha R, Oestreicher E, Ochoa-Maya M, Roubsanthisuk W, Williams GH, Adler GK.  Cardiac damage prevention by eplereonone:  comparison with low sodium diet or potassium loading.  Hypertens 2002, 39(part 2): 641-618.
3. Oestreicher EM, Martinez-Vasquez D, Stone JR, Jonasson L, Roubsanthisuk W, Mukasa K, and Adler GK.  Aldosterone and not PAI-1 is a critical mediator of early AngII/L-NAME-induced myocardial injury. Circulation, 2003,108: 2517-2523.
4. Guo Z, Kherde S, Adler GK.  Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease.  Current Opinion in Endocrinology and Diabetes. In press.

Contact Information:
Phone : (617) 732-5661
gadler@partners.org