Key Points
- To determine the localization of type 1 angiotensin II receptor subtypes (AT1A and AT1B) and evaluate their intracellular calcium mobilization across rat glomeruli and nephron segments.
- Assessed AT1A and AT1B mRNA distribution across microdissected rat glomeruli and nephron segments using reverse transcription-PCR.
- Measured angiotensin II-evoked intracellular calcium ([Ca2+]i) mobilization via Fura-2 fluorescence with and without external calcium, testing inhibition using losartan and PD 123319.
- AT1A mRNA was dominant throughout nephron segments (~84%), whereas glomeruli displayed equal expression of AT1A and AT1B mRNA.
- Angiotensin II (10^-7 mol/L) provoked the greatest [Ca2+]i rise in proximal segments (delta ~300 to 400 nmol/L) and thick ascending limbs (delta ~200 nmol/L), with similar median effective concentrations in glomeruli (12.2 nmol/L) and cortical thick ascending limbs (10.3 nmol/L).
- Calcium responses were completely blocked by losartan (1 µmol/L) but unaffected by PD 123319 (1 µmol/L), with intracellular pools contributing significantly to peak response magnitude.
Structured PICO
PPopulationRat kidney (microdissected glomeruli and nephron segments)
IInterventionAngiotensin II (Ang II) with or without AT1 receptor antagonist losartan or AT2 antagonist PD 123319
OOutcomeLocalization of AT1A and AT1B mRNA and variations in intracellular calcium ([Ca2+]i) elicited by Ang IIsurrogate
This preclinical study demonstrates that AT1A is the predominant angiotensin II receptor subtype in rat nephron segments, and both AT1A and AT1B similarly activate calcium mobilization.