Key Points
- To determine whether defective coupling of dopamine-1 receptors to adenylate cyclase occurs in the proximal convoluted tubules of Dahl salt-sensitive rats.
- Microdissected proximal convoluted tubules from Dahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats maintained on either a low-NaCl or high-NaCl diet.
- Measured adenylate cyclase activity in tubular segments stimulated with selective dopamine-1 agonists (fenoldopam at 10⁻⁷ M, SND-919-C12 at 10⁻⁶ M) and direct activator forskolin (10⁻⁵ M).
- Fenoldopam (10⁻⁷ M) and SND-919-C12 (10⁻⁶ M) failed to stimulate adenylate cyclase activity in the proximal convoluted tubules of DSS rats on both low- and high-NaCl diets.
- In DSR rats, fenoldopam and SND-919-C12 stimulated adenylate cyclase activity by 289–320% and 220–270%, respectively, across both low- and high-NaCl diets.
- Forskolin (10⁻⁵ M) effectively increased adenylate cyclase activity across all four experimental groups regardless of strain or dietary salt intake.
Structured PICO
PPopulationDahl salt-sensitive (DSS) and Dahl salt-resistant (DSR) rats on low- or high-NaCl diet
IInterventionSelective D1 agonists (fenoldopam 10(-7) M and SND-919-C12 10(-6) M) and forskolin (10(-5) M)
CComparatorDSR rats vs DSS rats; low- vs high-NaCl diet
OOutcomeAdenylate cyclase (AC) activity in the proximal convoluted tubule (PCT)surrogate
Dahl salt-sensitive rats exhibit a defect in dopamine-1 receptor coupling to adenylate cyclase in the proximal tubule that precedes blood pressure elevation.