Document Detail


Early decline in the catecholamine release-inhibitory peptide catestatin in humans at genetic risk of hypertension.
MedLine Citation:
PMID:  12131530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hypertension is a complex trait with an ill-defined genetic predisposition, in which adrenergic mechanisms seem to be involved even at the early stages. Chromogranin A is a pro-hormone stored and released with catecholamines by exocytosis; its fragment catestatin, formed in vivo, inhibits further catecholamine release as an antagonist at the physiologic trigger for secretion, the neuronal nicotinic cholinergic receptor. METHODS: We measured catestatin by radioimmunoassay in n = 277 subjects stratified by blood pressure (n = 61 hypertensive, n = 216 normotensive), and if normotensive by genetic risk of developing hypertension: family history positive (n = 176) versus negative (n = 40). Maximum likelihood analysis tested for bimodality. Involvement of catestatin in pathophysiology was probed by measurements of catecholamines and leptin, and the hemodynamic responses to environmental (cold) stress. RESULTS: The normotensive offspring of patients with hypertension already had diminished catestatin (P = 0.024), and family history was a better predictor of catestatin than age, ethnicity or gender (P = 0.014). Greater catestatin variance among family history-positive individuals (P = 0.021) suggested heterogeneity in this group, and a bimodal distribution (P < 0.001) identified 4.3% of individuals in a lower mode of catestatin values, all with positive family histories (P = 0.05). Catestatin correlated inversely with body mass index (r = -0.215, r(2) = 0.046, n = 276, P < 0.001) and plasma leptin (r = -0.203, r(2) = 0.041, n = 212, P = 0.003), while body mass index and leptin correlated directly (r = 0.59, r(2) = 0.350, n = 212, P < 0.001). Family history-positive individuals had greater epinephrine excretion (P = 0.037) in addition to diminished catestatin, suggesting an inhibitory effect of catestatin on chromaffin cells in vivo. Low plasma catestatin predicted enhanced pressor response to a sympathoadrenal stressor (cold stress; r = -0.184, r(2) = 0.034, n = 211, P = 0.007), suggesting an adrenergic mechanism whereby diminished catestatin might predispose to later development of hypertension. In white subjects, diminished catestatin also predicted greater systemic vascular resistance responses to cold stress (r = -0.307, r(2) = 0.094, n = 75, P = 0.007), a relationship not found in Blacks (r = 0.122, r(2) = 0.015, n = 94, P = 0.243). CONCLUSIONS: We conclude that catestatin is diminished early in the course of development of hypertension, even in the normotensive offspring of patients with the disease. Low catestatin predicts augmented adrenergic pressor responses, suggesting a mechanism whereby diminished catestatin might increase the risk for later development of hypertension.
Authors:
Daniel T O'Connor; Mala T Kailasam; Brian P Kennedy; Michael G Ziegler; Noboru Yanaihara; Robert J Parmer
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of hypertension     Volume:  20     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-19     Completed Date:  2003-01-23     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1335-45     Citation Subset:  IM    
Affiliation:
Department of Medicine and Center for Molecular Genetics, University of California and V.A. San Diego Healthcare System, San Diego, California, USA. doconnor@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
California
Catecholamines / genetics*,  metabolism*
Chromogranin A
Chromogranins / blood*,  genetics*
Cold Temperature
Female
Genetic Markers / genetics
Genetic Predisposition to Disease / genetics
Hemodynamics / genetics
Humans
Hypertension / blood*,  ethnology,  genetics*
Leptin / blood
Male
Middle Aged
Multivariate Analysis
Obesity / blood,  genetics
Peptide Fragments / blood*,  genetics*
Predictive Value of Tests
Statistics as Topic
Stress, Physiological
Time Factors
Chemical
Reg. No./Substance:
0/Catecholamines; 0/Chromogranin A; 0/Chromogranins; 0/Genetic Markers; 0/Leptin; 0/Peptide Fragments; 0/chromogranin A (344-364)

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