In the heart, we are currently exploring the relationship between signal transduction and the control of local metabolism. We are focusing on the nitric oxide-cyclic GMP signal transduction system, which acts as a "brake" on myocardial function. This system exerts significant control of oxygen supply/consumption through direct effects on myocytes and vascular smooth muscle. We are attempting to determine the mechanisms through which this system operates and how problems like myocardial infarction, heart failure and obesity affect the responses to this system.
In the brain, excitatory amino acids, such as glutamate, increase cerebral oxygen consumption. The relative importance of the various glutamate receptors in the control of cerebral metabolism is not known. Activation of these receptors also affects cerebral blood flow. How the relationship between cerebral oxygen supply and consumption is affected by these receptors is not known. We also wish to determine the importance of the various receptor subtypes in the control of cerebral metabolism during stroke. Excess activation of these receptors leads to excitotoxicity.