The neuropeptides, vasopressin and oxytocin, are present in brain stem regions important in cardiovascular regulation. Results show that the spontaneously hypertensive rat (SHR) exhibits a specific deficit in these neuropeptides; with the changes occurring in the paraventricular nucleus and brain stem. Thus, brain peptides, in particular the neurohypophyseal hormones, may be important in the control of cardiovascular homeostasis and possibly in the etiology of hypertension. We propose to investigate the mechanisms controlling both blood pressure, and vasopressin and oxytocin synthesis. A protocol for the study of biosynthesis has been established; it involves the incorporation of a labeled amino acid, purification by molecular weight and high performance liquid chromatography (HPLC) and identification by immunochemical techniques. The synthesis of the high molecular weight precursors, neurophysins and the peptides will be determined in specific brain regions, namely, the magnocellular nuclei, median eminence, posterior pituitary and brain stem. The goals of the project are: 1) To investigate hypothalamic and neurohypophyseal peptide biosynthesis in genetic hypertension (SHR). This is designed to evaluate the changes in peptidergic activity associated with the development of the high blood pressure, and 2) To assess the possible relationship between the high blood pressure and the changes in central peptidergic activity. The SHRs will be treated with the antihypertensive drug, propranolol, and the effects on blood pressure and neurohypophyseal peptides determined. This research proposal is based on the hypothesis that the central neuropeptides, vasopressin and oxytocin, may act as neurotransmitters or neuromodulators, and may be important in the control of blood pressure. Furthermore, derangements in this axis may be critical in the development of the increased blood pressure of the SHR. The results from these experiments should answer basic questions on the role of hypothalamic neuropeptides in the regulation of cardiovascular function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030845-02
Application #
3341862
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Morris, M; Alexander, N (1989) Baroreceptor influences on oxytocin and vasopressin secretion. Hypertension 13:110-4
Alexander, N; Morris, M (1988) Effects of chronic sinoaortic denervation on central vasopressin and catecholamine systems. Am J Physiol 255:R768-73
Morris, M; Alexander, N (1988) Baroreceptor influences on plasma atrial natriuretic peptide (ANP): sinoaortic denervation reduces basal levels and the response to an osmotic challenge. Endocrinology 122:373-5
Hattori, T; So, G M; Morris, M et al. (1988) Effect of central hypertonic stimulation on plasma atrial natriuretic peptide and oxytocin in conscious rats. Regul Pept 23:271-8
Buckalew, V M; Morris, M; Hamilton, R W (1987) Atrial natriuretic factor. Adv Intern Med 32:1-25
Blizard, D A; Morris, M (1987) Acute stress increases plasma concentrations of atrial natriuretic peptides. Proc Soc Exp Biol Med 184:123-6
Alexander, N; Melmed, S; Morris, M (1987) Suppressed serum prolactin in sinoaortic-denervated rats. Am J Physiol 252:R290-3
Morris, M; Eskay, R L; Sundberg, D K (1986) A tissue culture model for the study of peptide synthesis and secretion from microdissected hypothalamic explants. Methods Enzymol 124:359-71
Sundberg, D K; Dunlap 3rd, C E (1986) Methods for estimating the contribution of proenkephalin A and proenkephalin B input to neuronal areas. Methods Enzymol 124:617-26
Morris, M; Sundberg, D K; Bennett, B A (1986) Biochemical and immunochemical studies of supraoptic and paraventricular cultures. Hypertension 8:II168-73

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