Document Detail


Nerve growth factor enhances calcitonin gene-related peptide expression in the spontaneously hypertensive rat.
MedLine Citation:
PMID:  11230364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Calcitonin gene-related peptide (CGRP) expression is markedly reduced in dorsal root ganglia neurons in the spontaneously hypertensive rat (SHR). This decrease in such a potent vasodilator may contribute to the elevated blood pressure. Therefore, the purpose of this study was to determine whether stimulation of neuronal CGRP expression in SHR, by means of the administration of nerve growth factor, would lower the blood pressure. Nerve growth factor (10 nmol/L per kg/d, IP) was given to 12-week SHR (n=8 to 11/group) once a day for 1, 3, and 7 days. Control SHR received vehicle only. All rats were instrumented for CGRP receptor antagonist (CGRP(8-37)) administration (intravenous) and mean arterial pressure recording. Both the 1- and 3-day NGF treatments lowered the mean arterial pressure to 147+/-5 and 147+/-3 mm Hg, respectively, compared with controls (166+/-3 mm Hg). However, by day 7, the mean arterial pressure had returned to control levels (169+/-5 mm Hg). CGRP(8-37) administration produced a significant mean arterial pressure increase in all 3 nerve growth factor-treated groups (14+/-2, 10+/-2, and 13+/-2 mm Hg). CGRP mRNA levels in dorsal root ganglia were increased in the 3 neurotrophin-treated groups, whereas CGRP peptide content was higher at days 3 and 7. Therefore, nerve growth factor treatment of SHR can enhance neuronal CGRP expression. At days 1 and 3, nerve growth factor produces a depressor response that is primarily mediated by CGRP as evidenced by the pressor effect of CGRP(8-37.) At day 7, CGRP also plays a counterregulatory role, even though the mean arterial pressure has returned to control levels. This finding may result from a nerve growth factor-mediated upregulation of a pressor system that counteracts the hypotensive actions of CGRP. Thus, these data suggest that the decreased production of CGRP in SHR could contribute to the hypertension.
Authors:
S C Supowit; H Zhao; D J DiPette
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  37     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-20     Completed Date:  2001-04-26     Revised Date:  2013-03-18    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  728-32     Citation Subset:  IM    
Affiliation:
Michigan State University, College of Human Medicine, Department of Medicine, East Lansing, Michigan, USA. scott.supowit@ht.msu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Blotting, Northern
Calcitonin Gene-Related Peptide / biosynthesis*,  genetics,  pharmacology
Ganglia, Spinal / metabolism*
Hypertension / etiology
Male
Nerve Growth Factor / pharmacology*
Neurons / metabolism
Peptide Fragments / pharmacology
RNA, Messenger / biosynthesis
Radioimmunoassay
Rats
Rats, Inbred SHR
Receptors, Calcitonin Gene-Related Peptide / antagonists & inhibitors
Time Factors
Up-Regulation
Grant Support
ID/Acronym/Agency:
HL-44277/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/RNA, Messenger; 0/Receptors, Calcitonin Gene-Related Peptide; 119911-68-1/calcitonin gene-related peptide (8-37); 83652-28-2/Calcitonin Gene-Related Peptide; 9061-61-4/Nerve Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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