Hypertension is a complex disease involving many pathophysiological changes. Important among those changes are alterations in neural and humoral regulation as well as in cell membrane characteristics. Eight principal investigators from 6 departments (3 clinical and 3 pre-clinical) have joined to study these changes. Animal models will include genetic hypertensive rats, DOCA hypertensive rats, sheep, and pigs, the obese dog and the dog to which an increase in lower body pressure is applied. Projects are designed to study the changes which occur during the development of these forms of hypertension and during its recession, when the initiating factors are removed. The goal is to assemble data relevant to the mechanisms responsible for the arterial pressure elevation. Among the specific variables measured will be ion fluxes across membranes, hormone levels (renin, aldosterone, ADH, cortisol, catecholamines) vascular reactivity, central nervous system effects and secretory processes of chromaffin cells. From these integrated projects a better understanding of the initiating factors and sequence of events leading to hypertension will emerge.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL018575-15
Application #
3097656
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1976-05-01
Project End
1991-06-30
Budget Start
1990-05-01
Budget End
1991-06-30
Support Year
15
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Rocchini, Albert P; Yang, John Q; Smith, Marla J et al. (2010) Serial changes in norepinephrine kinetics associated with feeding dogs a high-fat diet. J Clin Hypertens (Greenwich) 12:117-24
Kamal, Mohamed A; Keep, Richard F; Smith, David E (2008) Role and relevance of PEPT2 in drug disposition, dynamics, and toxicity. Drug Metab Pharmacokinet 23:236-42
Duan, Sheng Zhong; Ivashchenko, Christine Y; Whitesall, Steven E et al. (2007) Direct monitoring pressure overload predicts cardiac hypertrophy in mice. Physiol Meas 28:1329-39
Hu, Yongjun; Shen, Hong; Keep, Richard F et al. (2007) Peptide transporter 2 (PEPT2) expression in brain protects against 5-aminolevulinic acid neurotoxicity. J Neurochem 103:2058-65
Ennis, Steven R; Keep, Richard F (2007) Effect of sustained-mild and transient-severe hyperglycemia on ischemia-induced blood-brain barrier opening. J Cereb Blood Flow Metab 27:1573-82
Shen, Hong; Ocheltree, Scott M; Hu, Yongjun et al. (2007) Impact of genetic knockout of PEPT2 on cefadroxil pharmacokinetics, renal tubular reabsorption, and brain penetration in mice. Drug Metab Dispos 35:1209-16
Xiang, Jianming; Chiang, Pei-Pei; Hu, Yongjun et al. (2006) Role of PEPT2 in glycylsarcosine transport in astrocyte and glioma cultures. Neurosci Lett 396:225-9
Ennis, S R; Keep, R F (2006) Effects of 2,4-dinitrophenol on ischemia-induced blood-brain barrier disruption. Acta Neurochir Suppl 96:295-8
Carello, Katari A; Whitesall, Steven E; Lloyd, Mary C et al. (2006) Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats. Am J Physiol Heart Circ Physiol 290:H209-16
Xiang, Jianming; Hu, Yongjun; Smith, David E et al. (2006) PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res 1122:18-23

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