The goal of this project is to test if propagation of local vasomotor responses contributes to the regulation of cerebral blood flow and to further understand how local cerebral blood flow is matched to momentary metabolic needs of functional neural units within the cerebral cortex. Experiments will be performed in vitro. Rat cerebral penetrating arterioles will be isolated, transferred into an organ bath and cannulated. The vessels will be stimulated locally by microapplication of vasoactive agonists to induce vasodilation or vasoconstriction. With a video dimensional system or by computer aided video imaging vessel diameter will be measured at the site of stimulation and 500 and 1000 mu m away from the site of stimulation. This will determine whether the local vasomotor response is propagated. With intracellular recording electrodes the membrane potential of cells the vessel wall will be measured. It will be determined if (a) the change of the vessel diameter is accompanied by a change in cell membrane potential, and (b) the propagation of the vasomotor response is conducted through a change of the membrane potential spread longitudinally along the vessel. Testing will determine whether blocking the release of endothelial relaxation factor (EDRF) by chemically impairing the endothelium with N-nitro-L-- arginine (NOLA) or hemoglobin will influence the propagation of local vasomotor response. These studies will provide new information about regulatory control mechanisms and pathways of the brain circulation. Such information may be crucial in the understanding of pathologic malfunction of the brain circulation, such as loss of cerebral autoregulation after head injury or ischemia induced through subarachnoid hemorrhage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS030555-02
Application #
2268509
Study Section
Neurology A Study Section (NEUA)
Project Start
1993-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62
Osei-Owusu, Patrick; Knutsen, Russell H; Kozel, Beth A et al. (2014) Altered reactivity of resistance vasculature contributes to hypertension in elastin insufficiency. Am J Physiol Heart Circ Physiol 306:H654-66
Murata, Takahiro; Dietrich, Hans H; Xiang, Chuanxi et al. (2013) G protein-coupled estrogen receptor agonist improves cerebral microvascular function after hypoxia/reoxygenation injury in male and female rats. Stroke 44:779-85
Osei-Owusu, Patrick; Sabharwal, Rasna; Kaltenbronn, Kevin M et al. (2012) Regulator of G protein signaling 2 deficiency causes endothelial dysfunction and impaired endothelium-derived hyperpolarizing factor-mediated relaxation by dysregulating Gi/o signaling. J Biol Chem 287:12541-9
Dietrich, Hans H (2012) Cell-to-cell communication and vascular dementia. Microcirculation 19:461-7
Dietrich, Hans H; Abendschein, Dana R; Moon, Sung Ho et al. (2010) Genetic ablation of calcium-independent phospholipase A(2)beta causes hypercontractility and markedly attenuates endothelium-dependent relaxation to acetylcholine. Am J Physiol Heart Circ Physiol 298:H2208-20
Dietrich, Hans H; Horiuchi, Tetsuyoshi; Xiang, Chuanxi et al. (2009) Mechanism of ATP-induced local and conducted vasomotor responses in isolated rat cerebral penetrating arterioles. J Vasc Res 46:253-64
Ellsworth, Mary L; Ellis, Christopher G; Goldman, Daniel et al. (2009) Erythrocytes: oxygen sensors and modulators of vascular tone. Physiology (Bethesda) 24:107-16
Dietrich, Hans H (2007) Apolipoprotein E in hypercholesteremia and beyond. Stroke 38:2036
Horiuchi, Tetsuyoshi; Dietrich, Hans H; Hongo, Kazuhiro et al. (2003) Comparison of P2 receptor subtypes producing dilation in rat intracerebral arterioles. Stroke 34:1473-8

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