Department of Cell Biology and Neuroscience
Nelson Lab, Room B222
Piscataway, NJ 08854
The major objective of our research is to determine the roles of physiologically important regulators in the control of coronary circulation and ventricular rhythmicity. Our main focus has been on the role of the adenine nucleoside. adenosine. We have also examined regulators such as estrogen. We routinely use hypoxia and ischemia and reperfusion to challenge the heart before and after interventions designed to augment or attenuate the actions of adenosine, estrogen, etc. We have shown that adenosine deaminase (ADA), the enzyme that inactivates adensine by removing an amino group from the purine ring, is a good research tool for investigating the regulatory roles of adenosine. For example, we hypothesized that myocardial release of adenosine contributes significantly to the coronary vasodilation caused by regional hypoxia in the anesthetized, instrumented dog. To test this hypothesis, we pretreated dogs with commercially-available ADA before causing regional myocardial hypoxia. Coronary circulatory responses to hypoxia were significantly attenuated in the presence of administered ADA. In more recent years we hypothesized a role for adenosine in the ventricular arrhythmias caused by systemic hypoxia. Using administered ADA, we saw a significant reduction in the incidence of ventricular arrhythmias caused by hypoxia. Blocking the actions of endogenous ADA with erythro-9-(2-hydroxy. 3-nonyl) adenine (EHNA) significantly increased the incidence of hypoxia-induced ventricular arrhythmias. Most recently. we have found that the acute pretreatment of dogs (both male and female) with estrogen markedly and significantly attenuates the ventricular arrhythmias caused by regional myocardial ischemia and reperfusion. We plan to continue these lines of research in the future.