Ca⁺⁺ influx is essential for the hypotensive response to arginine vasopressin-induced neuron activation of the area postrema in the rat

We attempted to relate the signal pathway to the hypotension induced by arginine vasopressin (AVP) injection into the area postrema (AP) in urethane-anesthetized and ventilated rats with vagotomy. A femoral artery and vein were catheterized to measure the blood pressure (BP) and administer drugs, respectively. The rat was placed on a stereotaxic apparatus to expose the calamus sriptorius (CS) by craniostomy and maintained at normocapnia in hyperoxia. In protocol 1, hypotension evoked by AVP (3.0 × 10^{- 5} IU) microinjected into the AP 0.2 mm rostral to the CS of the midline was abolished by V_1A antagonist, U73122 (phospholipase C blocker), and BAPTA-AM (Ca⁺⁺ chelator), suggesting that an increasing intracellular Ca⁺⁺ is essential for AVP-induced hypotension. In protocol 2, AVP-induced hypotension was abolished by EGTA (extracellular Ca⁺⁺ chelator) and Ca⁺⁺ blockers such as nifedipine, nimodipine (L-types), and omega-conotoxin MVIIC (P/Q-type), but not by omega-conotoxin GVIA (N-type). In protocol 3, AVP-induced hypotension was blocked by calphostin C (protein kinase C inhibitor) and mimicked by an increase in intracellular K⁺ ions that was reversed by EGTA. Vehicle injections produced no changes in BP. In protocol 4, glutamate-induced hypotension was reversed by BAPTA-AM but not by EGTA or V_1A antagonist. Our data suggest that AVP-induced hypotension depends on Ca⁺⁺ influx through a signal pathway from phospholipase C to protein kinase C which inactivates K⁺ channels that may depolarize AP neurons to activate L- and P/Q-type Ca⁺⁺ channels. This may provide new insights into establishing a relationship between the signal pathway and physiological functions.