Dr. Joshi’s current interests are in cardiovascular biology that includes signaling by nitric oxide (NO), modulation of bio-transport mechanisms in hypertensive rat model. At present actively collaborating with Dr. Nikolaos Tsoukias.
Arginine, classified as a conditionally essential amino acid, is sold over-the-counter as a nutritional supplement that has been linked to enhanced immunity, increased muscle mass and reversing atherosclerosis. Its role in these beneficial effects is not clearly understood. Cellular L-arginine concentrations greatly exceed the amount necessary to maintain steady-state production of nitric oxide (NO) from nitric oxide synthase. However, in a phenomenon known as the arginine paradox, NO synthesis depends on externally administered L-arginine. The structural similarity between the arginine molecule’s guanidinium group and imidazoline compounds that are ligands for α-2 adrenergic and/or imidazoline receptors, suggest the possible involvement of receptor in the actions of arginine (Fig.1). We are interested in delineating the underlying mechanism of L-arginine mediated NO formation and vessel relaxation.
|Figure 1. Schematic of proposed arginine-mediated activation of eNOS NO synthesis. Extracellular arginine binding at the receptor turns on a signal transduction cascade through calcium entry, leading to elevated NO formation.|
In addition, studies are also carried out to study the defects in molecular mechanisms that manifest the widely prevalent disease condition, vascular hypertension or blood pressure. We use different molecular techniques to study the changes in expression levels of various membrane transport channels using a salt-sensitive hypertensive rat model. These investigations may ultimately lead to therapeutic intervention or treatment for this debilitating disease.
Key Words: Cardiovascular, hypertension, cell culture, nitric oxide, free radicals.
Edgar A. Jaimes, Run-Xia Tian, Mahesh S. Joshi, Leopoldo Raij. “Nicotine augments glomerular injury in a rat model of acute nephritis” Am J Nephrol., 29, 319, 2009
Arlin B. Blood, Mauro Tiso, Shilpa T. Verma, Jennifer Lo, Lawrence D. Longo, Mahesh S. Joshi, Ivan Azarov, Mark T. Gladwin, Daniel B. Kim-Shapiro, and Gordon G. Power. “Increased nitrite reductase activity of fetal versus adult ovine hemoglobin” Am J Physiol Heart Circ Physiol 296: H237-H246, 2009
Mahesh S. Joshi, T. Bruce Ferguson, Jr., Fruzsina K. Johnson, Robert A. Johnson, Sampath Parthasarathy, and Jack R. Lancaster, Jr., “Receptor-mediated activation of Nitric oxide synthesis by arginine in endothelial cells” Proc.Natl.Acad.Sci., USA 104, 9982, 2007.
Rozalina Grubina, Zhi Huang, Sruti Shiva, Mahesh S. Joshi, Ivan Azarov, Swati Basu, Lorna A. Ringwood, Alice Jiang, Neil Hogg, Daniel B. Kim-Shapiro, and Mark T. Gladwin, “Concerted Nitric Oxide Formation and Release from the Simultaneous Reactions of Nitrite with Deoxy- and Oxy-hemoglobin” J. Biol. Chem., 282, 12916, 2007.
Mahesh S. Joshi, T. Bruce Ferguson, Jr., Tae H. Han, Daniel R. Hyduke, James C. Liao, Tienush Rassaf, Nathan Bryan, Martin Feelisch, and Jack R. Lancaster, Jr., “Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions” Proc.Natl.Acad.Sci., USA 99, 10341, 2002.