Tag Archives: hypertension

A Brief Introduction

This post dates to last October, but I thought it would be worth re-posting over here since I’ve migrated in that time.  It’s an extended abstract of my research project that I submitted to the Charlotte Life Sciences conference last Fall.  I was among ten finalists selected from a pool of 20 regional universities to present our work to a panel of scientific advisors, business strategists, and private equity investors.  I doubted I had much of a shot of winning the $1,000 first place prize, but it did allow me to write about what exactly I study in a language that people outside the ivory tower (mine is actually brick) can somewhat understand.  Which is sort of exactly what I’d like to do with my career, only to a much greater extent than how it is “simplified” below.

I’m posting my introduction here mostly for posterity.  It’s fleshed out way more than it would be for my usual audience of cardiovascular scientists.  However, I am exceedingly proud that my former theatre major friend kind of understood what I wrote with the help of a few definitions.  If you’re particularly curious and/or bored, feel free to read on and learn how some of your tax dollars have been used the past few years:

————————-

Endocannabinoid Modulation of Baroreflex Sensitivity in a Model of Renin-Angiotensin System-Dependent Hypertension

As of 2012, one in 3 U.S. adults is hypertensive, defined as having a resting blood pressure greater than 140/90 millimeters of mercury.  While hypertension itself is asymptomatic, the statistics of cardiovascular diseases are startling: 69% of patients with a first heart attack, 77% with a first stroke, and 74% with congestive heart failure are hypertensive.  In 2008 the estimated direct and indirect cost of managing high blood pressure, including medications, doctor visits and hospital admissions, was $50.6 billion, up from $43.5 billion the previous year.  Hypertension thus represents a massive health and economic burden.

Despite significant advances in the ability to manage high blood pressure, its root causes remain elusive.  The two components of the autonomic nervous system, the sympathetic and parasympathetic nervous systems, have emerged as prime research targets for their role in blood pressure regulation.  Hypertension is usually accompanied by an autonomic imbalance in which the sympathetic nervous system predominates over the parasympathetic branch.  Some direct consequences of this imbalance include elevation of circulating sympathetic hormones, increased blood vessel constriction, increased heart rate, and reduced baroreflex sensitivity.

The impairment of baroreflex sensitivity (BRS) for control of heart rate, measured as the reduction of heart rate in response to increases in blood pressure, often precedes the onset of hypertension.  The arterial baroreflex is the primary feedback control system for the short-term regulation of blood pressure and is an important indicator of vagus nerve function.  The effectors of the baroreflex are the baroreceptors: stretch-sensitive mechanoreceptors concentrated in the walls of the aortic arch and carotid sinus that can detect changes in blood pressure.

Baroreceptors are innervated by fibers of the vagus and glossopharyngeal nerves, which make their first synapse at the solitary tract nucleus (NTS) of the brainstem, a major autonomic integration center.  When arterial pressure increases, baroreflex afferent neurons transmit excitatory signals to the NTS.  The NTS will then increase downstream activity of the vagus nerve, yielding a decrease in heart rate to help return blood pressure to resting baseline.  Therefore, identification of biological factors that may influence BRS is critically important for understanding the development of hypertension and other negative cardiovascular outcomes.

Tonic upregulation of the endocannabinoid system, endogenous compounds that act at the same receptors as marijuana, is strongly associated with hypertension and its risk factors.  The endocannabinoid system is a ubiquitous cellular signaling system that modulates cellular activity in peripheral organs and the central nervous system.   CBcannabinoid receptors, the principal neuronal target of the endocannabinoids, are densely expressed on nerve terminals in the NTS.  Previous studies show cannabinoid ligands, such as delta-9-THC and the endogenous cannabinoid anandamide, can modulate neuronal activity within the NTS via CB1 receptors.  Therefore, we hypothesized that activation of NTS CBreceptors would alter BRS for control of heart rate in live, normotensive Sprague-Dawley rats.  We further hypothesized that we would find evidence of upregulated CBreceptor tone in the NTS of a monogenetic model of hypertension, the (mRen2)27 rat, contributing to impaired baseline BRS in this strain.

——————

Essentially, I study how marijuana-like molecules in your brain affect your body’s control of blood pressure and heart rate.  And if you’re wondering, yes, smoking up chronically does interfere with your body’s ability to do this.  If you’re also wondering, no, I do not have access to weed in the lab. (That’s the most common question I get asked at conferences)

Advertisements