Hindawi Publishing Corporation Cardiology Research and Practice Volume 2012, Article ID 319230, 6 pages doi:10.1155/2012/319230 Research Article Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model Barry J. Connell, 1 Bobby V. Khan, 1, 2, 3 Desikan Rajagopal, 2 and Tarek M. Saleh 1 1 Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 2 InVasc Therapeutics, Atlanta, GA 30084, USA 3 Atlanta Vascular Research Foundation, 3562 Habersham at Northlake, Atlanta, GA 30084, USA Correspondence should be addressed to Bobby V. Khan, bobby.khan@atlantaclinicalresearch.com Received 1 July 2011; Revised 19 September 2011; Accepted 1 October 2011 Academic Editor: Anjali Arora Copyright © 2012 Barry J. Connell et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1–50mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5–10 mg/kg) and INV-161 (1–10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction. 1. Introduction Hypertension prevalence is highly variable among popu- lations worldwide. In the United States there is a dispro- portionate burden of this disease and its complications in African Americans [1]. African Americans have the highest prevalence of hypertension in the world, significantly higher than people of African origin living outside the United States [2]. According to the 2003-2004 National Health and Nutri- tion Examination Survey (NHANES) hypertension preva- lence is 39.1% in African Americans and 28.5% in White Americans [3]. The increased prevalence of hypertension in African-Americans has been attributed to both genetic and environmental factors [4]. Additionally, hypertension is usually observed at a younger age in African-Americans and it results in more severe disease complications. This results in a significantly higher hypertension related mortality rate for African Americans, 49.9% and 40.6% for African American men and women, respectively, compared to 17.9% for the overall US population in 2004 [1]. Cardiometabolic syndrome, a constellation of common cardiovascular risk factors (obesity/overweight, atherogenic dyslipidemia, glucose intolerance, and elevated blood pres- sure) has been shown to directly increase atherosclerotic car- diovascular disease [5]. Of particular interest is the im- portant role of the endothelium in vascular homeostasis. Endothelial changes are considered precursors to early chan- ges in the atherosclerotic endothelium leading to chronic diseases including cardiometabolic syndrome. Patients are often prescribed antihypertensive drugs such as captopril in an attempt to lower their risk for cardiovascular disease [6]. In addition, patients diagnosed with this syndrome would