Abstract

The purpose of this proposal is to illuminate the role that membrane-bound peptides play in the overall regulation of the brain angiotensin system. The proposal utilizes a multidisciplinary approach to investigate this problem and as such includes biochemical, behavioral, electrophysiological, and immunocytochemical studies. Several specific questions related to the overall theme are addressed. These include the following: 1) What is the active form of brain angiotensin? 2) What are the functional and biochemical characteristics of membrane-bound angiotensinases? 3) What are the biochemical characteristics of solubilized and purified angiotensin receptors and are they associated with peptidase activity? 4) Can modifications of peptidase activity alter the response of angiotensin-dependent effector mechanisms? And 5) When angiotensin degradation is blocked, does brain angiotensin turnover reflect the physiological state of the animal?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032063-06
Application #
3343295
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-07-01
Project End
1991-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Washington State University
Department
Type
Schools of Veterinary Medicine
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164

  Publications

Batt, C M; Jensen, L L; Harding, J W et al. (1996) Microinfusion of aminopeptidase M into the paraventricular nucleus of the hypothalamus in normotensive and hypertensive rats. Brain Res Bull 39:235-40
Hall, K L; Venkateswaran, S; Hanesworth, J M et al. (1995) Characterization of a functional angiotensin IV receptor on coronary microvascular endothelial cells. Regul Pept 58:107-15
Wright, J W; Hamilton, T A; Harding, J W (1995) Anomalous effects of losartan on aminopeptidase-induced reductions of blood pressure in SHR. Brain Res Bull 36:169-74
Wright, J W; Harding, J W (1994) Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. Neurosci Biobehav Rev 18:21-53
Miller-Wing, A V; Hanesworth, J M; Sardinia, M F et al. (1993) Central angiotensin IV binding sites: distribution and specificity in guinea pig brain. J Pharmacol Exp Ther 266:1718-26
Cook, V I; Grove, K L; Speth, R C et al. (1993) Differences between perinatal angiotensin binding in the brains of SHR and WKY rats. Regul Pept 45:395-405
Roberts, K A; Wright, J W; Harding, J W (1993) GABA and bicuculline-induced blood pressure changes in spontaneously hypertensive rats. J Cardiovasc Pharmacol 21:156-62
Wright, J W; Roberts, K A; Stubley, L A et al. (1993) Hypothalamic angiotensin release in response to AII or glutamic acid stimulation of the SFO in rats. Brain Res Bull 31:649-54
Hall, K L; Hanesworth, J M; Ball, A E et al. (1993) Identification and characterization of a novel angiotensin binding site in cultured vascular smooth muscle cells that is specific for the hexapeptide (3-8) fragment of angiotensin II, angiotensin IV. Regul Pept 44:225-32
Hanesworth, J M; Sardinia, M F; Krebs, L T et al. (1993) Elucidation of a specific binding site for angiotensin II(3-8), angiotensin IV, in mammalian heart membranes. J Pharmacol Exp Ther 266:1036-42

Showing the most recent 10 out of 62 publications