Grant: Operating Grant

Persistently high blood pressure is a prevalent problem among the population, also common in obesity, ultimately posing major risk factors for stroke, myocardial infarction and kidney failure. Identifying causes is difficult, so efforts to reduce blood pressure over the long term have become a clinical objective. In humans, as in experimental models of chronic hypertension, over activity in the sympathetic nerves to many organs (e.g. kidney) and to blood vessels suggests that the brain cells forming these pathways are "hyperactive", possibly indicating reduction in the "brake" that controls the sympathetic nervous system. Designing therapeutic approaches to target selectively these components of the nervous system would seem a reasonable goal. Achieving this objective needs more a focused approach based on an understanding of the cellular and molecular mechanisms that underlie the principles governing sympathetic nerve activity. To this end, we use a rodent model to acquire information specifically from the spinal neurons that give rise to the sympathetic outflow pathways to the cardiovascular system, kidneys and adrenal glands. We are particularly interested in nitric oxide (NO), a gas-like molecule that is best known for its actions to reduce angina when taken under the tongue. NO is made in sympathetic neurons in the spinal cord, and our preliminary data indicate that it may serve as the "brake" to control sympathetic nerve activity. Assessing how this molecule works selectively on these spinal neurons may aid in the design of a drug that could target these neurons selectively, much as nitroglycerin does for the heart, and have a therapeutic value in the long term control of hypertension.