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Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
Catecholamine storage vesicle protein expression in genetic hypertension
D T O'Connor1, M A Takiyyuddin, M P Printz
1Department of Medicine, Center for Molecular Genetics, University of California, V.A. San Diego Healthcare System, USA. doconnor@ucsd.edu
Chromogranin A (CgA) is elevated in human hypertension and in spontaneously hypertensive rats (SHR). In SHR, a single gene locus controls CgA, but it is not linked to blood pressure. CgA over-expression is variable in genetic hypertension.
Area of Science:
- Genetics and Molecular Biology
- Cardiovascular Physiology
- Endocrinology
Background:
- Chromogranin A (CgA) expression is heritable in humans.
- Elevated plasma CgA and augmented adrenal/neuronal pools are observed in human essential hypertension.
- CgA is investigated as a potential intermediate phenotype for complex traits like hypertension.
Purpose of the Study:
- To evaluate chromogranin A (CgA) expression in the spontaneously hypertensive rat (SHR) as a model for essential hypertension.
- To investigate the genetic control of CgA expression in relation to blood pressure in hypertensive rat models.
Main Methods:
- Measured plasma and adrenal CgA levels, adrenal norepinephrine, and dopamine beta-hydroxylase activity in SHR and Wistar Kyoto (WKY) rats.
- Analyzed CgA mRNA expression in the SHR adrenal medulla.
- Conducted genetic crosses (SHR x WKY) to assess the genetic basis of CgA phenotype and its linkage to blood pressure.
Main Results:
- Plasma and adrenal CgA were elevated in SHR compared to WKY rats, even at early ages.
- Adult SHR adrenal glands showed increased CgA and norepinephrine, but diminished dopamine beta-hydroxylase activity.
- Genetic analysis in F2 offspring suggested a single major locus controls adrenal CgA phenotype in SHR, but this locus is not linked to blood pressure.
Conclusions:
- Over-expression of chromogranin A is a variable characteristic of mammalian genetic hypertension.
- In the SHR model, CgA over-expression is primarily governed by a single genetic locus.
- The CgA locus itself is not directly associated with the blood pressure elevation observed in SHR.
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