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Dopamine D(3) receptors and salt-dependent hypertension
Gerd Luippold1, Claudia Zimmermann1, Matthias Mai1
1Department of Pharmacology, University of Tübingen, Tübingen, Germany.
Journal of the American Society of Nephrology : JASN
|October 25, 2001
Summary
Impaired dopamine D(3) receptors contribute to salt-dependent hypertension. Blocking these receptors induced hypertension in salt-resistant rats, suggesting a deficiency is a key factor.
Area of Science:
- Nephrology
- Pharmacology
- Cardiovascular Research
Background:
- Dopaminergic system alterations may influence hypertension development.
- Dopamine D(3) receptors are implicated in regulating sodium balance and hemodynamics in rodents.
Purpose of the Study:
- To investigate the role of dopamine D(3) receptors in salt-dependent hypertension.
- To compare D(3) receptor function and expression in salt-sensitive and salt-resistant rats.
Main Methods:
- Clearance experiments in anesthetized salt-sensitive (DS) and salt-resistant (DR) Dahl rats on normal and high-sodium diets.
- Administration of D(3) receptor agonist (7-OH-DPAT) and antagonist (BSF 135170).
- Measurement of glomerular filtration rate (GFR) and urinary sodium excretion; assessment of [(3)H]-7-OH-DPAT binding.
Main Results:
- D(3) receptor agonist increased GFR and natriuresis in DR rats, but not in hypertensive DS rats.
- Diminished D(3) receptor function in DS rats correlated with lower receptor binding.
- D(3) receptor blockade induced significant hypertension in DR rats on a high-salt diet.
Conclusions:
- Renal dopamine D(3) receptor expression and function are impaired in salt-sensitive Dahl rats.
- D(3) receptor deficiency is a significant pathophysiological factor in salt-dependent hypertension.
- Blocking D(3) receptors can induce salt-dependent hypertension, even in genetically resistant rats.