Grant: $381,841 - National Institutes of Health - Jul. 16, 2009
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Award Description: The human cutaneous circulation is an accessible, representative vascular bed for in vivo examination of mechanisms that contribute to vascular dysfunction with essential hypertension (HT). This proposal is a logical extension of our previous work investigating the vascular mechanisms underlying age and hypertensive-related changes in the control of reflex-mediated increases in skin blood flow. The proposed studies expand our previous research by pairing state-of-the-art nitric oxide (NO) specific in vivo methodologies (local heating and intradermal microdialysis) with in vitro analysis of human skin samples to examine the precise signaling mechanisms underlying impaired cutaneous vasodilatory (VD) signaling in humans with HT. The proposed investigation will pair in vivo and in vitro methodologies to examine the putative link between inflammation, oxidant stress, and NO production in the cutaneous vasculature of humans with HT.
Project Description: Specific Aim 1 will examine the NOS isoforms mediating attenuated cutaneous NO-dependent, Specific Aim 2 will examine the role of arginase in regulating L-arginine availability for NO synthesis through the constitutive NOSs, and Specific Aim 3 will examine roles of oxidative stress and cofactor BH4 availability as they relate to NOS uncoupling. We will also examine the mechanistic link between upregulated arginase and BH4 deficiency on NOS uncoupling by measuring real time relative oxidant production. PUBLIC RELEVANCE: One quarter of the population in the United States has undiagnosed or is being treated for essential hypertension. This health issue is pervasive and exacts emotional, physical, and financial costs. The results from these proposed studies will provide new and important information on the vascular effects of hypertension in the skin. Further, these results will provide insight into the regulation of skin blood flow and potential therapeutic intervention strategies for hypertensive vascular pathology.
Jobs Summary: One Principal Investigator (PI), two Research Faculty (Co-PI) positions, and two part-time technicians were assigned to work on this research project. One part-time graduate student and one part-time coordinator postions were created to work on this project. This will provide an opportuntity to expand experience and knowledge, and work-study, while facilitating the objectives of the project. (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Jul. 16, 2009. Help expand these official descriptions using the wiki below.