Abstract

Recent work from our laboratory has identified a new angiotensin-like peptide and its accompanying receptor system. This peptide, generated in vitro from 125I-Angiotensin III (AIII) by CNS membrane preparations, accounts for all the angiotensin specific binding activity seen in the brains of several mammalian species including gerbil, African Green monkey, and rabbit. The focus of this proposal is to establish the in vivo relevance of this new brain peptide system. The work described addresses several important questions: 1. Is the AIII derived peptide (A3DP) found endogenously? 2. How do in vivo levels of A3DP compare with those of other known angiotension peptides, specifically AII and AIII? 3. What is the distribution of A3DP throughout the CNS? 4. Is the A3DP found in vivo the same as that isolated from in vitro preparations? Determining whether this system exists endogenously should provide the insight required to develop new and more effective antihypertensive agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032063-02
Application #
3343292
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
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