. The overall goal of this PPG since its inception in 1982 has been to achieve an understanding of the long-term regulation of arterial pressure and the consequences of high blood pressure. The studies are focused upon the regulation of body fluid volume by the kidneys and the regulation of systemic arterial vascular resistance This grant contains five interwoven scientific projects. Project 1 examines how excess production of reactive oxygen species (ROS) in inbred salt-sensitive Dahl rats (SS/Mcw) affects NO production within the renal medulla and the functional consequences of these interactions on the regulation of medullary blood flow, sodium homeostasis and arterial pressure. Project 12 will determine if a deficiency in L-arginine transport in the kidney of SS/Mcw rats contributes to the decreased availability of NO, elevation in ROS, and reduced excretory function. Project 3 will determine if pressure natriuresis is mediated through changes in renal interstitial hydrostatic pressure with an increased production of 20-HETE and/or EETs in the proximal tubule and 20-HETE in the thick ascending limb of Henle. Project 10 will determine whether the low ANG11 levels seen in Dahl salt-sensitive rats are responsible for the impaired response of cerebral arteries to vasodilator stimuli and if these impaired responses involve the endothelium or receptors in the vascular smooth muscle cells. Project 13 will study the role of locally produced ANG11 and the interaction between ANG11, NO, and 20-HETE in the regulation of microvessel density. Each of these projects will utilize unique genetic inbred strains (consomic and congenic lines) that provide the trait of interest and a genetically defined control strain. Three core units Administrative, Biochemistry/Analytical, and Research Services will support and facilitate the research in this program. The program reflects a long-standing experience of shared ideas and techniques that has provided a synergistic environment for advancing our understanding of arterial blood pressure regulation and hypertension.
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