Angiotensin II inhibition of Ca2+ currents is independent of ATR1 angiotensin II receptor activation in rat adult vagal afferent neurons

Angiotensin II (ANG II) has the ability to modulate the activity of neurons involved in the cardiovascular regulation. One effective way of doing that is by changing calcium currents. In the present study, we investigated the effects of ANG II on high-voltage-activated (HVA) Ca2+ currents measured in adult vagal afferent neurons using the whole-cell patch-clamp technique. In addition, we demonstrated the presence of ATR1 and ATR2 receptors mRNA at nodose neurons using conventional reverse transcriptase–polymerase chain reaction (RT–PCR). ANG II (100 nM) decreased the HVA Ca2+ current (peak current recorded at 0 mV: −60.9±8.7 pA/pF in control conditions versus −31.9±5.7 pA/pF in the presence of ANG II) and shifted the Ca2+ current activation to a more negative membrane potential (control V0.5=−12.5±1.5 mV versus −18.4±2.8 mV during perfusion with ANG II). Losartan (500 nM) was not able to prevent the ANG II effect on the HVA Ca2+ current making unlikely the involvement of the ATR1 receptor. When ANG II was perfused in the continuous presence of saralasin, a non-selective ANG II receptor antagonist, we observed a faster but transient inhibition of HVA Ca2+ current. The inhibition was not sustained as observed when we applied ANG II alone and the HVA Ca2+ current recovered with time reaching levels close to the control. Unexpectedly, treatment with the ATR2 blocker PD 123,319 (500 nM) caused a significant inhibition on the HVA Ca2+ current making rather difficult any further conclusions. The above results allow us to conclude that ANG II induced inhibition on the HVA Ca2+ current is probably not via ATR1 receptor activation.