PMID- 10803489
OWN - NLM
STAT- MEDLINE
DCOM- 20000619
LR  - 20191103
IS  - 0803-7051 (Print)
IS  - 0803-7051 (Linking)
VI  - 8
IP  - 5-6
DP  - 1999
TI  - Catecholamine storage vesicle protein expression in genetic hypertension.
PG  - 285-95
AB  - Chromogranin A expression is heritable in humans, and both plasma chromogranin A 
      concentration and its releasable adrenal and sympathetic neuronal pools are 
      augmented in established essential (hereditary) hypertension. To evaluate 
      chromogranin A further as a simpler or "intermediate phenotype" in the complex 
      trait of hypertension, we studied chromogranin A expression in the spontaneously 
      hypertensive rat (SHR), a rodent model of essential hypertension. Both plasma (p 
      < 0.0001) and adrenal medullary (p = 0.003 to p < 0.0001) chromogranin A were 
      elevated in the SHR, even at the earliest stages (3-4 weeks of age). In the adult 
      adrenal gland, both chromogranin A (p=0.005) and norepinephrine (p=0.011) were 
      increased in the SHR, while dopamine beta-hydroxylase activity was diminished (p 
      < 0.0001). Chromogranin A mRNA expression was also elevated in the SHR adrenal 
      medulla (p = 0.017). Differences in chromogranin A processing were not noted 
      between SHR and Wistar Kyoto control (WKY) rats. In an SHR x WKY genetic 
      intercross, control of the adrenal chromogranin A phenotype by a single major 
      locus was suggested by comparison of phenotypic variance of the F2 vs F1 
      generations, and by bimodal frequency histogram (3:1 ratio), confirmed by maximum 
      likelihood analysis (chi2 = 74.6, p < 0.000001) in the F2 generation. However, 
      microsatellite alleles at a surrogate locus (Ighe) 12.7 cM from chromogranin A 
      (Chga), on rat chromosome 6, failed to co-segregate with blood pressure in an F2 
      generation (F = 0.06, p = 0.94). In another rodent model of hereditary 
      hypertension, the genetically hypertensive mouse (BPH/2), adrenal chromogranin A 
      (p=0.018) and norepinephrine (p = 0.004) were actually diminished. We conclude 
      that over-expression of chromogranin A is a variable feature of mammalian genetic 
      hypertension. In one rodent model (the SHR), over-expression of chromogranin A is 
      largely controlled by a single genetic locus, but the chromogranin A locus itself 
      is not directly linked to determination of the blood pressure elevation of the 
      SHR.
FAU - O'Connor, D T
AU  - O'Connor DT
AD  - Department of Medicine, Center for Molecular Genetics, University of California, 
      V.A. San Diego Healthcare System, USA. doconnor@ucsd.edu
FAU - Takiyyuddin, M A
AU  - Takiyyuddin MA
FAU - Printz, M P
AU  - Printz MP
FAU - Dinh, T Q
AU  - Dinh TQ
FAU - Barbosa, J A
AU  - Barbosa JA
FAU - Rozansky, D J
AU  - Rozansky DJ
FAU - Mahata, S K
AU  - Mahata SK
FAU - Wu, H
AU  - Wu H
FAU - Kennedy, B P
AU  - Kennedy BP
FAU - Ziegler, M G
AU  - Ziegler MG
FAU - Wright, F A
AU  - Wright FA
FAU - Schlager, G
AU  - Schlager G
FAU - Parmer, R J
AU  - Parmer RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Blood Press
JT  - Blood pressure
JID - 9301454
RN  - 0 (Catecholamines)
RN  - 0 (Chromogranin A)
RN  - 0 (Chromogranins)
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adrenal Medulla/metabolism
MH  - Animals
MH  - Base Sequence
MH  - Catecholamines/metabolism
MH  - Chromogranin A
MH  - Chromogranins/*genetics/metabolism
MH  - Crosses, Genetic
MH  - DNA Primers/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Hypertension/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Phenotype
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
EDAT- 2000/05/10 09:00
MHDA- 2000/06/24 11:00
CRDT- 2000/05/10 09:00
PHST- 2000/05/10 09:00 [pubmed]
PHST- 2000/06/24 11:00 [medline]
PHST- 2000/05/10 09:00 [entrez]
AID - 10.1080/080370599439508 [doi]
PST - ppublish
SO  - Blood Press. 1999;8(5-6):285-95. doi: 10.1080/080370599439508.