Document Detail


Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog.
MedLine Citation:
PMID:  16007257     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished catestatin might increase the risk for hypertension. We generated Chga and humanized mice through transgenic insertion of a human CHGA haplotype in order to probe CHGA and catestatin in vivo. Chga mice displayed extreme phenotypic changes, including: (a) decreased chromaffin granule size and number; (b) elevated BP; (c) loss of diurnal BP variation; (d) increased left ventricular mass and cavity dimensions; (e) decreased adrenal catecholamine, neuropeptide Y (Npy), and ATP contents; (f) increased catecholamine/ATP ratio in the chromaffin granule; and (g) increased plasma catecholamine and Npy levels. Rescue of elevated BP to normalcy was achieved by either exogenous catestatin replacement or humanization of Chga mice. Loss of the physiological "brake" catestatin in Chga mice coupled with dysregulation of transmitter storage and release may act in concert to alter autonomic control of the circulation in vivo, eventuating in hypertension.
Authors:
Nitish R Mahapatra; Daniel T O'Connor; Sucheta M Vaingankar; Amiya P Sinha Hikim; Manjula Mahata; Saugata Ray; Eugenie Staite; Hongjiang Wu; Yusu Gu; Nancy Dalton; Brian P Kennedy; Michael G Ziegler; John Ross; Sushil K Mahata
Related Documents :
23711047 - Stress and antibiotics alter luminal and wall-adhered microbiota and enhance the local ...
6134527 - Rimorphin (dynorphin b) exists together with alpha-neo-endorphin and dynorphin (dynorph...
2344087 - Labetalol in the treatment of epinephrine overdose.
12655167 - Tnf-alpha rapidly antagonizes the beta-adrenergic responses of the chloride current in ...
21157927 - Priming with endotoxin increases acute lung injury in mice by enhancing the severity of...
25320317 - Murine cytomegalovirus is not restricted to the house mouse mus musculus domesticus: pr...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  115     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-11     Completed Date:  2005-08-31     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1942-52     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, UCSD, San Diego, CA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology
Chromaffin Granules / pathology,  physiology
Chromogranin A
Chromogranins / genetics*,  physiology*
Circadian Rhythm
Corticosterone / blood
Epinephrine / blood
Gene Targeting
Humans
Hypertension / etiology*,  genetics*,  pathology,  physiopathology
Hypertrophy, Left Ventricular / pathology
Mice
Mice, Knockout
Mice, Transgenic
Microscopy, Electron
Neuropeptide Y / blood
Norepinephrine / blood
Renin / blood
Grant Support
ID/Acronym/Agency:
DK 60702/DK/NIDDK NIH HHS; HD 39293/HD/NICHD NIH HHS; P01 HL58120/HL/NHLBI NIH HHS; R29 DA11311/DA/NIDA NIH HHS; U01 HL69758/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/CHGA protein, human; 0/Chromogranin A; 0/Chromogranins; 0/Neuropeptide Y; 0/chromogranin A, mouse; 50-22-6/Corticosterone; 51-41-2/Norepinephrine; 51-43-4/Epinephrine; EC 3.4.23.15/Renin
Comments/Corrections
Comment In:
J Clin Invest. 2005 Jul;115(7):1711-3   [PMID:  16007250 ]

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


Previous Document:  Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the d...
Next Document:  A peripheral circulating compartment of natural naive CD4 Tregs.