M. Julia Brosnan , Ph.D.

Staff Scientist, Ordway Research Institute
Assistant Professor, Center for Cardiovascular Science, Albany Medical College

Center for Metabolic Diseases

Telephone: (518) 641-6424
Fax: (518) 641-6304
jbrosnan@ordwayresearch.org

Research Focus

Oxidative stress has been implicated in the development of a number of cardiovascular diseases including hypertension, atherosclerosis and diabetes. The underlying mechanisms remain to be resolved but probably involve an excess production of superoxide (SO) which reacts with nitric oxide (NO) and not only reduces the amount of bioavailable NO but also produces the deleterious species peroxynitrite.

Genetic models of hypertension such as the Spontaneously Hypertensive Rat (SHR) and sub-strains such as the Stroke Prone Spontaneously Hypertensive Rat (SHRSP) allows these mechanisms to be investigated in a controlled environment. We have previously shown that the blood vessels of the SHRSP have much higher levels of superoxide than that of the normotensive control strain Wistar Kyoto.

Endothelial dysfunction manifest by the SHRSP can be manipulated in vivo using adenoviral gene transfer. Delivery of adenovirus encoding either superoxide dismutase (SOD) or nitric oxide synthase (NOS) resulted in an improvement in the bioavailability of nitric oxide in SHRSP.

The focus of my research is in determining the mechanisms in which oxidative stress contributes to the development of hypertension and diabetes in animal models and cell lines. We are investigating the therapeutic potential of anti-oxidants on vascular physiology and metabolism and measuring blood pressure parameters using radiotelemetry. We are also developing assays for agents designed to reduce the production of reactive oxygen species.

Selected Publications

Hamilton CA, Brosnan MJ, Al-Benna S, Berg G, Dominiczak AF. NAD(P)H oxidase inhibition improves endothelial function in rat and human blood vessels. Hypertension. 2002 Nov;40(5):755-62

Brosnan MJ, Hamilton CA, Graham D, Lygate CA, Jardine E, Dominiczak AF. Irbesartan lowers superoxide levels and increases nitric oxide bioavailability in blood vessels from spontaneously hypertensive stroke-prone rats. J Hypertens . 2002;20:281-6.

McBride MW, Carr FJ, Graham D, Anderson NH, Clark JS, Lee WK, Charchar FJ, Brosnan MJ, Dominiczak AF. Microarray analysis of rat chromosome 2 congenic strains. Hypertension . 2003;41:847-53

McBride M, Brosnan MJ (joint first authors) , Mathers J, McLellan, J, Miller WH, Graham D, Hanlon N, Hamilton C, Polke JM, Lee WK and Dominiczak AF. Reduction of GSTM1 expression in the SHRSP contributes to oxidative stress. Hypertension (2005) 45 1-7.

Miller WH, Brosnan MJ (joint first authors) Graham D , Nicol C, Morecroft I , Channon K , Danilov S , Reynolds PN , Baker A and Dominiczak AF. Targeting Endothelial Cells With Adenovirus Expressing Nitric Oxide Synthase Prevents Elevation of Blood Pressure in SHRSP. Mol Ther. (2005) 12 (2):321-7.

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