Endocrinology, Diabetes and Hypertension

Gordon Williams, M.D.

Dr. Williams’ group’s first major goal is the identification of the genetic underpinnings of endocrine factors related to cardiovascular (CV) risk in hypertension and diabetes. The research focuses on evaluating hormones that can modify vascular contractility and/or salt handling. The major current thrusts are the RAAS kallikrein, cortisol, adducin, the beta-2 adrenergic receptor and ion transport systems. The second major goal is to determine the role of aldosterone in producing CV disease at molecular, cellular, organ, whole animal and clinical levels.  Recent studies suggest that aldosterone has a wide range of effects including inducing microvascular ischemia, thrombosis, fibrosis, and inflammatory responses many of them potentially mediated by aldosterone’s interaction with caveolins. Techniques employed include whole animal physiological studies using normal animals, those made hypertensive and those genetically modified (e.g. knock-outs and transgenics). Molecular and cellular techniques include gene arrays using chip technology, proteomics, confocal microscopy, electrophysiology and in situ hybridization.

Selected References

1. Kurina LM, Weiss LA, Graves SW, Parry R, Williams GH, Abney M, Ober C.  Sex difference in the genetics of morning serum cortisol levels: genome wide screen identifies two novel loci specific to women.  J Clin Endocrinol Metab 90:4747-52, 2005
2. Gumieniak O, Hurwitz S, Perlstein TS, Ngumezi UC, Hopkins RN, Jeunemaitre X, Williams GH.  Aggregation of High-Normal TSH in Hypertensive Families.  J Clin Endocrinol Metab 90:5985- 90, 2005 
3. Fisher NDL, Hurwitz S, Jeunemaitre X, Hopkins PN, Hollenberg NK, Williams GH.  Familial aggregation of low-renin hypertension.  Hypertension 2002; 39:914-918.
4. Grant FD, Romero JR, Jeunemaitre X, Hunt SC, Hopkins PN, Hollenberg NH, Williams GH.  Low-renin hypertension, altered sodium homeostasis, and an alpha-adducin polymorphism.  Hypertension 2002; 39: 191-196
5. Hopkins PN, Hunt SC, Jeunemaitre X, Smith B, Solorio D, Fisher NDL, Hollenberg NK, Williams GH.  Angiotensin genotype affects renal and adrenal responses to angiotensin II in essential hypertension.  Circulation 2002; 105: 1921-1927.
6. Martinez DV, Rocha R, Matsumura M, Oestreicher E, Ochoa-Maya M, Roubsanthisuk W, Williams GH, Adler GK.  Cardiac damage prevention by eplerenone: comparison with low sodium diet or potassium loading.  Hypertension 2002; 39: 614-618.
7. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips R, Roniker B, Kleiman J, Krause S, Burns D, Williams GH.  Effects of eplerenone, enalapril and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: The 4E-LVH Study.   Circulation,  2003: 108: 1831-1838.
8. Kosachunhanun N, Hunt SC, Hopkins PN, Williams RR, Jeunemaitre X, Corvol P, Ferri C,  Mortensen RM, Hollenberg NK, Williams GH.  Genetic determinants of nonmodulating    hypertension.  Hypertension, 2003; 42: 901-908.