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Naomi Deidre Fisher
Associate Physician, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
75 Francis Street
Boston, MA 02115

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Research Narrative:

One major focus of my clinical research continues to be the interplay between endocrinology and renal and adrenal physiology, to unravel their interacting contributions to the syndromes of human hypertension. Specific research protocolsrevolve around pharmacological interruption of the renin-angiotensin-system at different levels, with the goal of determining its role in normal renal physiology and disease.Most recent physiologic studiesinvolve renin inhibition. This body of work has provided important evidence for the biological importance of intrarenal AngII. In addition, I have been concerned with the effect of race, gender and age on sensitivity to AngII. All of the physiologic studies above are complemented by genetic analyses.

A second major focus involves a related but new area: the vascular effects of flavanol-rich foodstuffs and nitric oxide. I am studying the cardiovascular effects of flavonoid-rich cocoa in healthy humans,which increases vascular reactivity via a nitric-oxide dependent pathway. Advancing age is associated with changes in cerebral blood flow (CBF) regulation which may threaten cerebral perfusion and ultimately contribute to functional disability as well as to impaired cognition. Potential corrective therapies are unknown.  Consumption of flavonoid-rich foods and beverages, including cocoa, tea and red wine, has been associated with a reduction in coronary events; our hypothesis credits the flavonoid compounds in these plant-derived drinks.  Cocoa can contain extraordinary concentrations of a flavonoid subset known as flavanols, shown to activate nitric oxide (NO) synthase.  In the peripheral circulation, we have demonstrated that cocoa rich in flavanols induced vasodilation, improving endothelial function in healthy people.  We also reported that flavanol-rich cocoa enhanced endothelial function to a greater degree among older than younger healthy adults. Through infusion of the specific NO synthase inhibitor L-NAME, we have demonstrated that the mechanism in the periphery is NO-dependent. In a recent study of healthy elderly, we showed that dietary intake of flavanol-rich cocoa is associated with a significant increase in cerebral blood flow velocity in the middle cerebral artery (MCA) as measured by transcranial Doppler (TCD). No mechanistic investigations have been conducted.  We propose physiologic studies to determine the mechanism underlying cerebral blood flow responsiveness and whether it, too, is NO- dependent. The trials will involve ingestion of a quality-controlled flavanol-rich cocoa product and mimetic as control, as well as parallel studies in the peripheral circulation.

University of Pennsylvania School of Meidicne, 1986

Publications (Pulled from Harvard Catalyst Profiles):

1. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Lobo MD, Sharp ASP, Bloch MJ, Basile J, Wang Y, Saxena M, Lurz P, Rader F, Sayer J, Fisher NDL, Fouassier D, Barman NC, Reeve-Stoffer H, McClure C, Kirtane AJ. Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control Following Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial. Circulation. 2019 Mar 17.

2. Fisher NDL, Fera LE, Dunning JR, Desai S, Matta L, Liquori V, Pagliaro J, Pabo E, Merriam M, MacRae CA, Scirica BM. Development of an entirely remote, non-physician led hypertension management program. Clin Cardiol. 2019 Feb; 42(2):285-291.

3. Fisher NDL, Curfman G. Hypertension-A Public Health Challenge of Global Proportions. JAMA. 2018 11 06; 320(17):1757-1759.

4. Beckman JA, Hurwitz S, Fisher NDL. Arginine impairs endothelial and executive function in older subjects with cardiovascular risk. J Am Soc Hypertens. 2018 10; 12(10):723-731.

5. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, Basile J, Kirtane AJ, Wang Y, Lobo MD, Saxena M, Feyz L, Rader F, Lurz P, Sayer J, Sapoval M, Levy T, Sanghvi K, Abraham J, Sharp ASP, Fisher NDL, Bloch MJ, Reeve-Stoffer H, Coleman L, Mullin C, Mauri L. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018 06 09; 391(10137):2335-2345.

6. Fisher NDL, Orav EJ, Chang G. Effects of alcohol consumption on blood pressure in hypertensive women. Am J Drug Alcohol Abuse. 2018; 44(2):200-205.

7. McMullan CJ, Borgi L, Curhan GC, Fisher N, Forman JP. The effect of vitamin D on renin-angiotensin system activation and blood pressure: a randomized control trial. J Hypertens. 2017 04; 35(4):822-829.

8. McMullan CJ, Borgi L, Fisher N, Curhan G, Forman J. Effect of Uric Acid Lowering on Renin-Angiotensin-System Activation and Ambulatory BP: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2017 May 08; 12(5):807-816.

9. Borgi L, McMullan C, Wohlhueter A, Curhan GC, Fisher ND, Forman JP. Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial. Hypertension. 2017 02; 69(2):243-248.

10. Borgi L, McMullan C, Wohlhueter A, Curhan GC, Fisher ND, Forman JP. Effect of Vitamin D on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial. Am J Hypertens. 2017 Feb; 30(2):124-129.