Nitric Oxide: Linking Oral and Systemic Health
Nathan S. Bryan, Ph.D.

Development of chronic hypertension has significant morbidity and mortality, and approximately 33% of adults over the age of 20 either have untreated hypertension or are taking medications to control high blood pressure. Human blood pressure regulation is complex, and despite decades of research into the variables affecting resting blood pressure, there is still a significant knowledge gap. One area ripe for investigation is the role of the human microbiome in blood pressure regulation. It is now recognized that the oral commensal bacteria have the potential to provide an important metabolic function in human physiology by contributing to the generation of nitric oxide (NO).  NO is an essential signaling molecule regulating cardiovascular physiology, and is produced in the human body by conversion of arginine to NO by endogenous nitric oxide synthase. The current paradigm of NO production/regulation focuses at the level of nitric oxide synthase (NOS), through the five-electron oxidation of L-arginine.  However, this pathway becomes dysfunctional with age and disease and the activity of eNOS varies by subject.  The existing literature indicates that oral microbial communities have the ability to supplement inadequate host NO production by participation in the enterosalivary nitrate-nitrite-NO pathway.  The enterosalivary nitrate-nitrite-NO pathway is the process by which dietary nitrate is reduced in the oral cavity into nitrite by bacterial nitrate reductase enzymes encoded by the oral flora. Nitrite can subsequently be further reduced by bacterial NO-producing nitrite reductase enzymes directly to NO, or can be converted chemically to NO when swallowed and exposed to stomach acid. Therapeutically, this strategy suggests that an effective strategy to promote NO production and overcome conditions of NO insufficiency may not be targeted at eNOS, but rather on targeting specific oral nitrate and nitrite reducing bacterial communities.  Understanding and harnessing this redundant compensatory pathway may prove to be a viable and cost-effective strategy.

Learning Objectives:

1. Learn about nitric oxide biochemistry and physiology
2. Understand how the oral microbiome is involved in nitric oxide production
3. To teach the attendees how to apply this information in the management of their patients to restore NO and normalize blood pressure

Dr. Bryan earned his undergraduate Bachelor of Science degree in Biochemistry from the University of Texas at Austin and his doctoral degree from Louisiana State University School of Medicine in Shreveport where he was the recipient of the Dean’s Award for Excellence in Research.  He pursued his post-doctoral training as a Kirschstein Fellow at Boston University School of Medicine in the Whitaker Cardiovascular Institute.  After a two-year post-doctoral fellowship, in 2006 Dr. Bryan was recruited to join faculty at the University of Texas Health Science Center at Houston by Ferid Murad, M.D., Ph.D., 1998 Nobel Laureate in Medicine or Physiology.  During his tenure as faculty and independent investigator at UT, his research focused on drug discovery through screening natural product libraries for active compounds.  His nine years at UT led to several discoveries which have resulted in over a dozen issued US and international patents and many more pending worldwide.

Dr. Bryan has been involved in nitric oxide research for the past 25 years and has made many seminal discoveries in the field.  He is a successful entrepreneur and Founder, Chairman and CEO of Bryan Therapeutics, Inc., a privately-held, clinical-stage biotechnology company that is actively engaged in the discovery and development of nitric oxide-based therapies.  BTI has active drug development programs in heart disease, Alzheimers’ Disease and topical drugs for diabetic ulcer and non-healing wounds. His  consumer line of products are some of the most successful nitric oxide products on the market.  Dr. Bryan is an international leader in molecular medicine and nitric oxide biochemistry.

1 CE credit available to AAPMD members