Catecholamine storage vesicle protein expression in genetic hypertension

Daniel T. O'Connor, Marwan A. Takiyyuddin, Morton P. Printz, Thai Q. Dinh, Juan A. Barbosa, David J. Rozansky, Sushil K. Mahata, Hongjiang Wu, Brian P. Kennedy, Michael G. Ziegler, Fred A. Wright, Gunther Schlager, Robert J. Parmer

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57 Scopus citations

Abstract

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 β-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 (χ2 = 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.

Original languageEnglish (US)
Pages (from-to)285-295
Number of pages11
JournalBlood Pressure
Volume8
Issue number5-6
DOIs
StatePublished - Jan 1 1999

Keywords

  • Adrenal medulla
  • Catecholamine
  • Chromaffin
  • Chromogranin
  • Dopamine β- hydroxylase
  • Hypertension
  • Secretogranin

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    O'Connor, D. T., Takiyyuddin, M. A., Printz, M. P., Dinh, T. Q., Barbosa, J. A., Rozansky, D. J., Mahata, S. K., Wu, H., Kennedy, B. P., Ziegler, M. G., Wright, F. A., Schlager, G., & Parmer, R. J. (1999). Catecholamine storage vesicle protein expression in genetic hypertension. Blood Pressure, 8(5-6), 285-295. https://doi.org/10.1080/080370599439508